3
Operations, Oversight, and Funding of Cancer Clinical Trials

Cancer clinical trials are highly complex and represent a major research undertaking. They require hundreds of steps with numerous decision points and there are multilayered and iterative review processes because multiple oversight bodies have jurisdiction over a trial. The primary focus of the Cooperative Group Program is large, definitive, randomized Phase III studies and the development efforts preceding these trials (NCI, 2006). Phase III trials are considered the “gold standard” for changing medical practice because the results of these trials are used to obtain Food and Drug Administration (FDA) approval, establish practice guidelines, and make insurance coverage decisions. They are also the most complex and costly trials to conduct. These large-scale clinical trials necessitate interactions among numerous stakeholders, including multiple governmental agencies, academic medical centers, community practices, patients, and industry. To improve the system as a whole, a revision of the roles of all these stakeholders must be considered.

This chapter describes the organization, oversight, and funding of the National Cancer Institute (NCI) Cooperative Group Program, as well as the processes and collaborations needed to develop, launch, and complete a large-scale cancer clinical trial. The chapter identifies inefficiencies and limitations of the current system and describes the committee’s recommendations, which aim to improve the speed, efficiency, and effectiveness of cancer clinical trials, especially those that the Cooperative Groups undertake.



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3 Operations, Oversight, and Funding of Cancer Clinical Trials Cancer clinical trials are highly complex and represent a major research undertaking. They require hundreds of steps with numerous decision points and there are multilayered and iterative review processes because multiple oversight bodies have jurisdiction over a trial. The primary focus of the Cooperative Group Program is large, definitive, randomized Phase III stud- ies and the development efforts preceding these trials (NCI, 2006). Phase III trials are considered the “gold standard” for changing medical prac- tice because the results of these trials are used to obtain Food and Drug Administration (FDA) approval, establish practice guidelines, and make insurance coverage decisions. They are also the most complex and costly trials to conduct. These large-scale clinical trials necessitate interactions among numerous stakeholders, including multiple governmental agencies, academic medical centers, community practices, patients, and industry. To improve the system as a whole, a revision of the roles of all these stakehold- ers must be considered. This chapter describes the organization, oversight, and funding of the National Cancer Institute (NCI) Cooperative Group Program, as well as the processes and collaborations needed to develop, launch, and complete a large-scale cancer clinical trial. The chapter identifies inefficiencies and limitations of the current system and describes the committee’s recom- mendations, which aim to improve the speed, efficiency, and effective- ness of cancer clinical trials, especially those that the Cooperative Groups undertake. 121

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122 A NATIONAL CANCER CLINICAL TRIALS SySTEM ORGANIzATION OF THE COOPERATIvE GROuP PROGRAM The Cancer Therapy Evaluation Program (CTEP), which is part of the Division of Cancer Treatment and Diagnosis (DCTD) of NCI, administers the Cooperative Group Program, which represents a major component of DCTD’s extramural research activities. The NCI Cooperative Groups were originally organized by geographic area or, in some cases, by type of disease or therapeutic modality. Each Cooperative Group includes a large network of physicians, statisticians, nurses, clinical research associates, pharmacists, patient advocates, and other affiliated investigators. The Groups operate independently and have their own administrative structures, operating pro- cedures, and committees. Each Group has an operations office and statisti- cal center overseen by the Group chair and Group statistician, respectively. To be involved with a Cooperative Group, institutions must apply for mem- bership and meet that Group’s eligibility criteria, including accrual potential and the ability to comply with Group standards and federal requirements. Each institution participating in a Cooperative Group is represented by a principal investigator, who manages the institution’s activities within the Group (Mauer et al., 2007). Institutions participate in the Cooperative Groups as main member institutions, affiliates of a main member institution, or members of par- ticipating Community Clinical Oncology Programs (CCOPs). The main member institutions are generally academic medical centers or other major medical centers that are centrally involved in Cooperative Group activities. Main member institutions enroll a significant number of patients in clinical trials and also contribute scientific expertise and other resources to Group activities. Affiliate members, designated by the main member institutions, include community-based organizations and physicians’ practices and have lower patient accrual rates. Created in 1983, “the CCOP network allows patients and physicians to participate in state-of-the-art clinical trials for cancer prevention and treat- ment while in their local communities,” according to NCI (2009b). The CCOP network can include hospitals, clinics, health maintenance organiza- tions, groups of practicing physicians, or a consortium that agrees to work with a principal investigator through a single administrative unit (Mauer et al., 2007). Each CCOP chooses to join one or more CCOP Research Bases, which are NCI-designated Cancer Centers or Cooperative Groups that design, develop, and conduct clinical trials (NCI, 2009b). OvERSIGHT OF CLINICAL TRIALS Cancer clinical trials are highly regulated activities. Multiple agencies of the U.S. Department of Health and Human Services (HHS) review and

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12 OPERATIONS, OVERSIGHT, AND FUNDING provide oversight of cancer clinical trials, including NCI, FDA, the Office for Human Research Protections (OHRP), and the Office for Civil Rights (OCR). Many reviews are required before a Cooperative Group clinical trial can begin. These include reviews undertaken by the disease site and other scientific committees of the Cooperative Groups, various committees and branches of NCI, institutional review boards (IRBs), comprehensive cancer centers, CCOPs and their affiliates, and, in some cases, FDA and industry sponsors (Table 3-1). Additional oversight is required during the conduct of the trial and at the closure of the trial. The many oversight bod- ies have different objectives and responsibilities, and thus, they seek similar and overlapping but not identical information and action for compliance. This section provides a brief overview of Cooperative Group clinical tri- TAbLE 3-1 Types of Reviews Required to Develop a Cooperative Group Clinical Trial, by Stakeholder CTCG CTEP CCC CCOP/Affiliates Others Scientific Disease Site Steering Protocol Feasibility Industry Review Committee Committee/ Review Review Sponsor CRM Executive Site Surveys Committee PRC Protocol CTEP Final Reviews (2–4) Data CRF Reviews CDE Review Management (2–4) Database Review Safety/Ethics Informed Local IRB Informed CIRB Consent Consent Regulatory Regulatory PMB Review FDA Review RAB Review Contracts/ Budget Industry Grants Language Sponsor Study Start-up Start-up Start-up Start-up Review Review Review NOTES: CCC = Comprehensive Cancer Centers; CCOP = Community Clinical Oncology Pro- gram; CDE = Common Data Element; CIRB = central institutional review board; CRF = case report form; CRM = Concept Review Meeting; CTCG = Clinical Trials Cooperative Group; CTEP = Cancer Therapy Evaluation Program; FDA = Food and Drug Administration; PMB = Pharmaceutical Management Branch; PRC = Protocol Review Committee; RAB = Regulatory Affairs Branch. SOURCE: Dilts, 2008.

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12 A NATIONAL CANCER CLINICAL TRIALS SySTEM als oversight, with emphasis on issues that the committee considered most relevant to improving the clinical trials system. NCI Oversight of Cooperative Group Trials The cooperative agreements that provide funding to the Cooperative Groups stipulate NCI review and oversight at each step of the clinical trial process, including selection of trials to be conducted, protocol development, and trial operations (NCI, 2006). The role of CTEP staff, as described in the NCI clinical trials Cooperative Group Program Guidelines (NCI, 2006), is to “assist, facilitate, and assure optimal coordination of Group activi- ties. CTEP staff have very specific and well-defined responsibilities for the oversight and review of Group clinical trials and for investigational agent development.” Given this central position of NCI in the clinical trials sys- tem, the committee recommends that the current roles of NCI as well as the Cooperative Groups be reevaluated. The 2005 report by the Clinical Trials Working Group (CTWG) rec- ommended several ways to improve NCI oversight of cancer clinical trials (NCI, 2005b; see also Appendix A). In response to the recommendations of the CTWG, NCI created a number of offices, committees, and subcom- mittees, as indicated in Table 3-2 and Figure 3-1. Trial Concept Selection Investigators within the Cooperative Groups develop ideas for new cancer clinical trials, and these suggestions percolate through Cooperative Group committees to the Group leadership. Funding for the Cooperative Groups is based on past accomplishments but is not provided on a per trial basis or on the basis of specific trial proposals (see the section on funding for cancer clinical trials). However, all trial concepts that the Groups gen- erate must be reviewed and approved by CTEP before they are launched. Because an excess of trials with poor enrollment raised concerns that priori- tization of the trials was inadequate, the CTWG recommended the creation of a network of scientific steering committees (Box 3-1) that would leverage Cooperative Group, inter-Group, Specialized Programs of Research Excel- lence, and Cancer Center structures to work with NCI staff on the design and prioritization of Phase III trials to better allocate resources, increase sci- entific quality, and reduce duplication (NCI, 2005b; see also Appendix A). With this new organizational setup, principal investigators submit the con- cept for a clinical trial to CTEP for review and approval by the appropriate steering committees, with the goal of prioritizing them. This approach to concept review remains inefficient and is not suf- ficiently effective in prioritizing trials. Since the steering committees were formed, the lengths of concept proposals have increased significantly (they

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12 OPERATIONS, OVERSIGHT, AND FUNDING TAbLE 3-2 NCI Oversight of Cancer Clinical Trials Office, Committee, or Subcommittee Role NCI Office, Coordinating Center Established in 2006; supports the implementation of for Clinical Trials the initiatives of the CTWG and the Translational Research Working Group (TRWG) NCI Committees Clinical and Translational Research Established in 2005; an internal committee that Operations Committee (CTROC) provides strategic oversight for NCI clinical trials and translational research Clinical Trials and Translational Established in 2007; provides extramural oversight for Research Advisory Committee implementation of the CTWG and TRWG initiatives, (CTAC) including steering committees CTAC Subcommittees/Working Groups Investigational Drug Steering Provides strategic input into the clinical development Committee (IDSC) (early phase) plans for new agents for which the Cancer Therapy Evaluation Program holds the investigational new drug application Disease-Specific Scientific Steering Prioritize concepts for Phase III and selected Phase II Committees (SCs) therapeutic clinical trials; refine and collaborate on concepts by the use of task forces, when appropriate Patient Advocate Steering Develops and shares best practices for patient Committee advocate participation in steering committees; identifies common concerns and needs and proposes potential solutions; disseminates information from steering committees to the appropriate communities; ensures that the concept evaluations consider the patient community at large and includes a special focus on minority and underserved populations The Clinical Trials Management Provides strategic advice for the CTMS work space, System (CTMS) Steering advising on project selection, prioritization, and Committee oversight Ad Hoc Coordination Provides advice on how to foster collaboration among Subcommittee the various components of the NCI-sponsored clinical trials infrastructure, to develop a fully integrated clinical trials system Ad Hoc Public/Private Partnership Provides advice on how to enhance NCI-sponsored Subcommittee clinical trials through collaborative interactions with the private sector Cooperative Group Clinical Trials Charged with developing a model for aligning Funding Model/Complexity Model reimbursement of Phase III treatment trials with Working Group complexity, to compensate the additional costs Correlative Science Working Charged with developing validation standards and Group prioritization criteria of correlative science studies associated with Phase III trials Operational Efficiency Working Charged with developing approaches to cut timelines Group in half

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12 A NATIONAL CANCER CLINICAL TRIALS SySTEM Extramural Clinical Trials Community Clinical Trials and Translational Research Advisory Committee (CTAC) Co ordinating Center for NCI Director Clinical T rials (CCCT) Clinical and Translational Research Operations Committee (CTROC) Divisions, Centers, and Offices FIGuRE 3-1 Integrated management of NCI cancer clinical trials. SOURCE: Doroshow, 2008. are now about 25 pages long), making the review process more arduous. Multiple layers of review still slow the process, and trial concepts are still not ranked against each other, as is usually done in peer review. Steer- ing committees review and vote up or down on trial concepts as they are submitted, and NCI staff actively participate in the review process, unlike other NCI peer review groups. As of January 1, 2010,1 62 percent of concepts for Phase III trials reviewed by the steering committees had been approved,2 whereas the historic approval rate was about 65 percent before 1 The various steering committees have been phased in gradually, with start dates as follows: Gastrointestinal Cancer, January 2006; Gynecologic Cancer, June 2006; Head and Neck Can- cer, January 2007; Genitourinary Cancer, February 2008; Breast, September 2008; Lung, Fall 2008; Hematologic Malignancies, December 2009. 2 Of 45 concepts, 28 (62 percent) were approved, 15 (33 percent) were disapproved, and 2 (4 percent) were pending.

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12 OPERATIONS, OVERSIGHT, AND FUNDING BOX 3-1 Clinical Trials and Translational Research Advisory Committee Steering Committees Investigational Drug Steering Committee (IDSC) for Early-Phase Trial Prioritization Membership includes principal investigators of NCI’s early-phase U01 grants and  N01  contracts  and  representatives  from  Cooperative  Groups  and  other  content  experts. The committee has nine task forces in the areas of signal transduction,  biomarkers,  angiogenesis,  clinical  trial  design,  pharmacology,  immunotherapy,  PI3K/Akt/mTOR  (PAM),  cancer  stem  cells,  DNA  repair,  and  programmed  cell  death. The Group has developed recommendations for: •  Toxicity management of antiangiogenic agents •  Novel Phase I and Phase II clinical trial designs •  Prioritization of agents for immunotherapy trials •  Guidelines for the incorporation of biomarkers into early-phase trials Disease-Specific Scientific Steering Committees NCI  established  disease-specific  scientific  steering  committees  with  the  goal  of  increasing information exchange at an early stage of trial development; increasing  the efficiency of clinical trial collaboration; reducing trial redundancy; and devel- oping, evaluating, and prioritizing trial concepts. These committees are charged  with prioritizing, refining, and collaborating on concepts for Phase III and selected  Phase II therapeutic clinical trials. The committees use task forces when appro- priate,  convene  planning  meetings  to  identify  the  critical  issues  and  questions  about the disease to be studied, and periodically review accrual and unforeseen  implementation issues.   The initial committees included the Gastrointestinal Cancer, Gynecologic Can- cer, and Head and Neck Cancer Committees. Subsequent committees included  the Genitourinary Cancer, Breast Cancer, and Thoracic Malignancy Committees  and three committees for adult Hematologic Malignancies (Leukemia, Lymphoma,  and Myeloma). Committees on brain cancers and pediatrics are in development.  The full transition to disease-specific steering committees is expected in 2010. SOURCES: NCI, 2009a,f. the implementation of the committees.3 The approval rate for Phase II trial concepts was 53 percent. In addition, there is little interaction among the disease-specific steering committees to determine trial priorities across disease categories, nor is there consideration of how the trial portfolio should be balanced with regard to Phase II or Phase III trials, although 3 Personal communication, Margaret Mooney, National Cancer Institute, December 9, 2009.

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12 A NATIONAL CANCER CLINICAL TRIALS SySTEM they are charged with guiding the development of “strategic priorities” (NCI, 2005b). A possible alternative approach might be for the steering committees to identify research priorities and then issue requests for pro- posals to address them. However, the trial concept review process should be strengthened and streamlined, and it should entail the evaluation of concise proposals (including the intended statistical design) that are ranked against each other. The emphasis should be on scientific strength and opportunity, innovation, feasibility, and importance to improving patient outcomes. In addition, steering committees should operate independently from NCI staff, with NCI taking a more traditional role of facilitating the review process rather than actively participating in it; and they should have a primary focus on the prioritization of clinical needs and scientific opportunities and on facilitating communication and cooperation among the Cooperative Groups. Protocol Development After CTEP approval for a trial concept is achieved, the principal inves- tigator and other key staff develop a full study protocol that must again be reviewed and approved by various branches within CTEP (Table 3-1). Although the Cooperative Group guidelines state that protocols can be “approved with recommendations,” in which investigators are requested to give serious consideration to any recommendation included in the consen- sus review but are not obligated to amend the study, reviewers generally do not distinguish between major and minor review concerns. The committee recommends that all review bodies distinguish between major review con- cerns (concerns regarding patient safety and critical scientific flaws, which must be addressed) and minor concerns (which should be considered, but are not obligatory). Moreover, if changes are made before activation of the study, the investigators must send CTEP a revised protocol for review that details any changes in the previous CTEP-approved document. This policy includes changes to the protocol that are requested by an IRB subsequent to CTEP approval (see also the section on oversight of trials by IRBs). Similarly, minor changes requested by NCI can trigger iterative reviews by IRBs. Additional duplicative and iterative reviews can further slow the process when a trial involves an investigational new drug (IND) or an investiga- tional device exemption (IDE), as both FDA and NCI are involved in pro- tocol review and development (see also the section on FDA oversight). The committee recommends that federal oversight be more flexible in allowing minor amendments to the protocol or consent form to fast-track the chain of reapprovals. In sum, the protocol development process is arduous and time-consuming.

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12 OPERATIONS, OVERSIGHT, AND FUNDING Months are often consumed by multiple re-reviews that sometimes address only minor changes. Given the funding limits and voluntary nature of the Cooperative Group Program, it can be difficult for the Groups to devote sufficient staff time to rapidly develop and amend a protocol as the process proceeds, further compounding delays due to expectations for revisions and re-review (IOM, 2009c). The provision of funds for professional project man- agers could ease the workloads of principal investigators and greatly facilitate a rapid review process and adherence to timelines. As described in subsequent sections of this chapter, improved processes are also needed to reduce the time required for protocol development and trial launch. For example, use of standardized templates for some portions of the protocol might result in fewer iterative reviews and speed the review process. Trial Operations Once a trial is launched, NCI takes a direct role in overseeing quality control, data and safety monitoring, data management and analysis, and compliance with federal regulatory requirements (NCI, 2006). For example, an NCI program director assisted by the Biometric Research Branch (BRB) staff assesses Cooperative Group compliance with NCI-established policies on data and safety monitoring boards for all Cooperative Group Phase III trials. At the request of CTEP, the BRB staff also review mechanisms established by the Cooperative Group for data management and analysis. BRB staff make recommendations with the goal of ensuring that data col- lection and management procedures are adequate for quality control and analysis yet are sufficiently simple to encourage maximum participation of physicians entering patients into studies and to avoid unnecessary expense. Data must be made available for external monitoring as well, as required by NCI’s agreement with FDA relative to NCI’s responsibility as sponsor of a therapeutic agent (NCI, 2006). The Clinical Trials Monitoring Branch (CTMB) of CTEP provides direct oversight of each Cooperative Group’s monitoring program, which includes on-site auditing. CTMB is responsible for establishing guidance for the conduct of quality assurance audits and for overseeing and monitoring the compliance of the Groups, the CCOP research bases, and the Cancer Trials Support Unit (CTSU) with NCI’s monitoring guidelines. CTMB also monitors compliance with applicable federal regulations. CTMB staff may attend certain on-site audits, and they review audit reports and findings and assess the adequacy and acceptability of any corrective actions. CTMB staff also review and provide advice regarding the mechanisms established by the Group for quality control of the therapeutic and diagnostic modalities that it uses in its trials (NCI, 2006). In addition to overseeing the conduct of Cooperative Group clinical

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10 A NATIONAL CANCER CLINICAL TRIALS SySTEM trials, NCI also provides some logistical support (NCI, 2006). For example, the Pharmaceutical Management Branch provides for the distribution of investigational new agents for which DCTD is the sponsor. However, NCI does not provide those services for other agents. Faster trials could be fostered through more active and consistent support from NCI. Thus, the committee recommends that NCI file more IND applications for agents to be tested in approved protocols and that NCI devote more funds to the dis- tribution of drugs for approved protocols to ensure an adequate drug sup- ply for high-priority studies. These tasks entail time- and resource-intense activities. An expanded support role for NCI would help Group investiga- tors gain access to more experimental therapeutic agents and reduce the time that the Groups spend in negotiation with industry to acquire agents before the launch of a trial and also ensure the availability of the agent during the trial. NCI could facilitate the more timely completion of clinical trials in other ways as well. NCI should provide resources and technical assistance to facilitate the rapid adoption of a common patient registration system. For example, the Oncology Patient Enrollment Network4 would provide a standardized Internet-based environment for the enrollment of all patients in all Cooperative Group trials. NCI should also provide a common remote data capture system.5 The availability of such a system would permit sites to enter patient-level data into a clinical database over the Internet. The implementation and adoption of these structured electronic tools would increase consistency across trials, Groups, and sites; conserve resources by reducing the workload associated with patient enrollment and follow-up; allow more timely data review; and enhance the knowledge gained from a trial. However, these transitions can be costly and temporarily disruptive, so support from NCI to facilitate rapid implementation is important. NCI should also facilitate the establishment of more efficient and timely methods for ensuring that trial data are complete and accurate while the trial is ongoing. Many Groups wait until completion of a trial before beginning the necessary steps to ensure data quality because they lack the resources to check the data more frequently, but this can result in significant delays in analyzing and publishing the results. NCI should also develop standardized case report forms that meet regulatory requirements. The language for most clinical data elements in NCI-sponsored trials has been standardized by the NCI Common Data Elements,6 but standardized report formats would also simplify the reporting across multiple trials and multiple sites. 4 See https://open.ctsu.org. 5 See https://www.ctsu.org/RDC_project_page.asp. 6 See https://wiki.nci.nih.gov/display/caDSR/CTEP+Common+Data+Elements.

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11 OPERATIONS, OVERSIGHT, AND FUNDING Oversight of Trials by IRbs In the 1970s, concern about the inadequate protection of human sub- jects in research led to federal regulations and the establishment of IRBs7 (Beecher, 1966; HEW, 1979). At that time, most clinical research was done at single sites by single investigators. Since then, the increasing emphasis on evidence-based clinical practice has greatly increased the number of clinical trials. There has also been substantial growth in the number of multicenter trials as well as an increase in the complexity of clinical trials. In addition, the purview of IRBs has been expanded as additional regulations regarding human subjects research have been developed, such as the Privacy Rule promulgated under the provisions of the Health Insurance Portability and Accountability Act (HIPAA). These combined changes have overburdened IRBs and have fostered long delays in the review of study protocols and informed-consent forms (ICFs) (IOM, 2002). IRB Oversight of Multicenter Trials In many cases, each site participating in a multicenter trial will have its own IRB review of a study, which causes “unnecessary duplication of effort, delays and increased expenses in the conduct of multi-center tri- als,” as noted in a recent FDA guidance (FDA, 2006). For example, one study (Greene and Geiger, 2006) found that one-quarter of the 20 trials reviewed experienced delays (of up to 8 months) because of multiple IRB negotiations. Multiple IRB reviews do not necessarily improve patient protection, as evidenced by the numerous inconsistencies in the rulings of local IRBs reviewing the same study (Gold and Dewa, 2005; Greene and Geiger, 2006). One survey of participating sites in a multicenter genetic epidemiology study found that the participating local IRBs used different evaluation criteria, which resulted in requirements for the use of different numbers of consent forms at each institution participating in the trial (McWilliams et al., 2003). Another analysis found that of 20 multicenter clinical trials reviewed, 17 experienced inconsistencies both in the IRBs’ review processes and in their recommendations (Greene and Geiger, 2006). McWilliams and colleagues concluded, “Lack of uniformity in the review process creates uneven human subjects protection and incurs considerable inefficiency” (McWilliams et al., 2003). The lack of consistency in consent requirements among IRBs can also lead to selection bias and decrease statistical power (Jamrozik, 2000). In addition, the bulk of the changes that IRBs request are often minor changes to ICFs that increase the reading level of the forms, thus making 7 45 C.F.R. § 46.103.

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10 A NATIONAL CANCER CLINICAL TRIALS SySTEM High-priority trials must be adequately funded to efficiently and effec- tively attain results that can move the field forward. NCI has an obligation to adequately fund trials identified as being of high priority. NCI should increase the total funding allocation for the Cooperative Group Program to ensure the effective translation of discoveries made with public fund- ing to improved clinical care. Thus, NCI should allocate a larger portion of its research portfolio to the Clinical Trial Cooperative Group Program to ensure that the Program has sufficient resources to achieve its unique mission. The allocation of NCI funds among the competing needs of its various programs is a major challenge for the NCI director, who must take many factors into consideration. Greater input from the broad expertise and experience of external advisory boards would be helpful to ensure the most rational distribution of funds across the major NCI programs, in light of such factors as scientific opportunity and clinical need. External advisory boards, such as the National Cancer Advisory board and the board of Scientific Advisors, should have a greater roles in advising NCI on how it allocates its funds to support a national clinical trials program. These high- level boards should not be involved in the oversight of individual trials or in concept review, which would further slow the process, but rather, they should have a greater influence on how much funding is allocated to the overall Cooperative Group Program. Given the limits of the NCI budget, the total number of NCI-funded trials undertaken by the Cooperative Groups should be reduced to a quan- tity that can be adequately supported, to ensure sufficient funding for high-priority trials. Compromising the science to launch more trials than the available funding can support is detrimental to progress. However, even in the absence of a substantial increase in the overall funding of the Program, the funds saved by launching fewer but higher-priority trials could be allocated for increased per case reimbursement rates to trial sites, which has been set at $2,000 since 1999, well below the estimated median costs per patient. The many duties required of clinicians and other key research staff to participate in clinical trials are costly in terms of both time and resources. These voluntary contributions constitute a substantial value and strength of the Program. However, when the discrepancy between the per case reimbursement and the actual cost of participation is excessive, as it is now, it becomes a major disincentive to participation. The existing system also often does not provide the resources required to thoroughly charac- terize each patient’s tumor and carefully match that profile to targeted therapeutics. Biomedical imaging and other biomarker tests are commonly becoming integral components of modern cancer clinical trials, but supple- mental funding for these tests must be obtained by the Cooperative Groups through other support mechanisms. Thus, NCI should increase the per case reimbursement and adequately fund highly ranked trials to cover the costs

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11 OPERATIONS, OVERSIGHT, AND FUNDING of the trial, including the costs of biomedical imaging and other biomarker tests that are integral to the trial design. Given the limited funding capacity of NCI, it would also be beneficial to leverage the resources of industry to support the work of the Cooperative Groups in a transparent way to benefit patients, for example, in compari- son trials or for secondary indications. Two recent reports from PCAST acknowledge the importance and value of strengthening public-private collaborations to enhance innovation, particularly for discovery and trans- lational research in personalized medicine. However, industry funding for Cooperative Group trials has been limited for a variety of reasons, includ- ing concern about the inherent inefficiencies in the Program and the groups’ concern about maintaining independence in study design and execution. These concerns may contribute to the increasing tendency of pharmaceuti- cal companies to conduct trials in other countries. Thus, NCI should facilitate the creation of more public-private partner- ships and precompetitive consortia, guided in part by successful models. NCI should also facilitate the development of appropriate hybrid funding models, in which NCI and industry support clearly defined components of trials that are of mutual interest. Commercial firms might be more interested in collaborations with the Cooperative Groups if the review and operational procedures of the Program were streamlined, as recommended in this report. However, novel hybrid funding mechanisms, as well as new efforts to establish public-private partnerships and precompetitive consortia would further aid progress toward effective collaboration, to the benefit of patients, who desire access to new and promising cancer therapies. Main- taining a critical mass of clinical trials in the United States via appropriate collaborations is important to ensure that patients in this country gain access to promising therapies as they develop, that trials address questions and generate data that are relevant and meaningful to patients in the United States, and that the nation retains a sufficient number of properly trained clinical trial specialists. REFERENCES AACI (Association of American Cancer Institutes). 2009. Association of American Cancer Institutes. http://www.aaci-cancer.org/ (accessed December 28, 2009). AAMC (American Association of Medical Colleges). 2006. National Conference on Alterna- tive IRB Models: Optimizing Human Subject Protection. http://www.aamc.org/research/ irbreview/irbconf06rpt.pdf (accessed April 7, 2009). AAMC. 2007a. Universal Use of Short and Readable Informed Consent Documents: How Do We Get There? http://www.aamc.org/research/clinicalresearch/hdickler-mtgsumrpt53007. pdf (accessed December 23, 2009).

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12 A NATIONAL CANCER CLINICAL TRIALS SySTEM AAMC. 2007b. Universal Use of Short and Readable Informed Consent Documents: How Do We Get There? Summary of Strategic Planning Meeting, May 0, 200. Washington, DC: Association of American Medical Colleges. Abrams, J. 2008a. NCI’s Central Institutional Review Board. Presented at the Director’s Con- sumer Liaison Group Meeting, Bethesda, MD. Abrams, J. 2008b. Organization of the NCI Clinical Trials System. Presentation to the National Cancer Policy Forum Workshop on Multi-Center Phase III Clinical Trials and the NCI Cooperative Groups, July 1, 2008, Washington, DC. Abrams, J., and M. Mooney. 2008. Memorandum on OHRP Regulations on Changes in Clini- cal Trial Informed Consent Documents and Continued Enrollment of New Participants. National Cancer Institute, Bethesda, MD, March 20. Abrams, J., R. Erwin, G. Fyfe, R. L. Schilsky, and R. Temple. 2009. Data Submission Stan- dards and Evidence Requirements. Presented at the Conference on Clinical Cancer Research, Panel 1. Engelberg Center for Health Care Reform, Brookings Institution, Washington, DC. ACS CAN (American Cancer Society Cancer Action Network). 2009. Barriers to Provider Participation in Clinical Cancer Trials: Potential Policy Solutions (draft). Washington, DC: American Cancer Society Cancer Action Network. Adler, J. 2009. NCI’s CIRB: Streamlining IRB Processes. Presentation to Cancer and Leukemia Group B Clinical Research Associates. http://www.calgb.org/Public/meetings/presenta tions/2009/summer_group/cra_cont_ed/03a_CIRB-Presentation_062009.pdf (accessed December 23, 2009). AHRQ (Agency for Healthcare Research and Quality). 2009. The AHRQ Informed Con- sent and Authorization Toolkit for Minimal Risk Research. http://www.ahrq.gov/fund/ informedconsent/ (accessed December 23, 2009). Amit, O., W. Bushnell, L. Dodd, R. Pazdur, N. Roach, and D. Sargent. 2009. Blinded Inde- pendent Central Review of PFS Endpoint. Presented at the Conference on Clinical Cancer Research, Panel 2. Engelberg Center for Health Care Reform, Brookings Institution, Washington, DC. Ansher, S., J. Abrams, and J. Cristofaro. 2009. Issues Related to the Revision of the IP Option in DCTD Sponsored Clinical Trials. Presented at the 9th Clinical Trials Advisory Com- mittee Meeting, Bethesda, MD. Barker, A. D., C. C. Sigman, G. J. Kelloff, N. M. Hylton, D. A. Berry, and L. J. Esserman. 2009. I-SPY 2: An adaptive breast cancer trial design in the setting of neoadjuvant che- motherapy. Clinical Pharmacology and Therapeutics 86(1):97–100. Beecher, H. K. 1966. Ethics and clinical research. New England Journal of Medicine 274(24):1354–1360. Benowitz, S. 2000. Children’s Oncology Group looks to increase efficiency, numbers in clinical trials. Journal of the National Cancer Institute 92(23):1876–1878. Bent, S., A. Padula, and A. L. Avins. 2006. Brief communication. Better ways to question patients about adverse medical events: A randomized, controlled trial. Annals of Internal Medicine 144(4):257–261. Blayney, D. W. 2009. Results of Cooperative Group Site Poll. Presented at the NCI National Cancer Advisory Board Meeting, September, Bethesda, MD. Breese, S., W. Burman, C. Rietmeijer, and D. Lezotte. 2004. The Health Insurance Portability and Accountability Act and the informed consent process. Annals of Internal Medicine 141(11):897–898. Bressler, L. R., and R. L. Schilsky. 2008. Collaboration between Cooperative Groups and industry. Journal of Oncology Practice 4(3):140–141.

OCR for page 121
1 OPERATIONS, OVERSIGHT, AND FUNDING Burman, W., S. Breese, N. Weis, J. Bock, A. Vernon, and Tuberculosis Trials Consortium. 2003. The effects of a local review on informed consent documents from a multicenter clinical trials consortium. Controlled Clinical Trials 24(3):245–255. caBIG (Cancer Biomedical Informatics Grid). 2007. Informed Consent Standardization and Simplification Projects. http://docs.google.com/gview?a=v&q=cache:VXz9ZL7sGnIJ: https://cabig-kc.nci.nih.gov/DSIC/uploaded_files/b/bb/Informed_Consent_Simplifica - tion_Projects.pdf+cabig,+informed+consent+standardization&hl=en&gl=us (accessed December 28, 2009). Campbell, F. A., B. D. Goldman, M. L. Boccia, and M. Skinner. 2004. The effect of format modifications and reading comprehension on recall of informed consent information by low-income parents: A comparison of print, video, and computer-based presentations. Patient Education and Counseling 53(2):205–216. CCCG (Coalition of Cancer Cooperative Groups). 2007. Informed Cancer Patient Consent. http://www.cancertrialshelp.org/Icare_content/icMainContent.aspx?intAppMode=10 (ac- cessed December 28, 2009). C-Change. 2005. A Guidance Document for Implementing Effective Cancer Clinical Trials: Version 1.2. Washington, DC: C-Change. C-Change and Coalition of Cancer Cooperative Groups. 2006. Enhancing Cancer Treatment Through Improved Understanding of the Critical Components, Economics and Barriers of Cancer Clinical Trials. Washington, DC: C-Change; Philadelphia, PA: Coalition of Cancer Cooperative Groups. C-Change and Coalition of Cancer Cooperative Groups. 2007. The Elements of Success: Conducting Cancer Clinical Trials: A Guide. Washington, DC: C-Change; Philadelphia, PA: Coalition of Cancer Cooperative Groups. CEO Roundtable on Cancer and NCI. 2008. Proposed Standardized Harmonized Clauses for Clinical Trial Agreements. Rockville, MD: CEO Roundtable on Cancer and NCI. Chase, R. B., and D. A. Tansik. 1983. The customer contact model for organizational design. Management Science 29(9):1037–1050. Cheng, S., M. Dietrich, S. Finnigan, A. Sandler, J. Crites, L. Ferranti, A. Wu, and D. Dilts. 2009. A sense of urgency: Evaluating the link between clinical trial development time and the accrual performance of CTEP-sponsored studies. Journal of Clinical Oncology 200 ASCO Annual Meeting Proceedings 27(18 Suppl.): CRA6509. Christel, M. 2009. More Muscle Needed for Regulatory Science. http://blog.rddirections.com/ index.php/2009/09/17/more-muscle-needed-for-regulatory-science (accessed November 3, 2009). CIBMTR (Center for International Blood and Marrow Transplant Research). 2008. Center for International Blood and Marrow Transplant Research. http://www.cibmtr.org (accessed December 8, 2009). CMRHC (Center for Management Research in Healthcare). 2009. Center for Management Research in Healthcare. http://www.cmrhc.org/ (accessed December 28, 2009). Coletti, A. S., P. Heagerty, A. R. Sheon, M. Gross, B. A. Koblin, D. Metzger, G. R. Seage, and International Conference on AIDS. 2003. Randomized controlled evaluation of a prototype informed consent process for HIV vaccine efficacy trials. Journal of Acquired Immune Deficiency Syndrome 32(2):161–169. CTAC (Clinical Trials Advisory Committee). 2008. th Clinical Trials Advisory Committee Meeting. http://deainfo.nci.nih.gov/advisory/ctac/0608/25jun08mins.pdf (accessed De- cember 28, 2009). CTEP (Cancer Therapy Evaluation Program). 1996. Clinical Trials Cooperative Group Pro- gram Guidelines. http://ctep.cancer.gov/resources/clinical/guidelines1-3.html (accessed November 19, 2008).

OCR for page 121
1 A NATIONAL CANCER CLINICAL TRIALS SySTEM CTSA (Clinical and Translational Award) Network. 2010. Clinical & Translational Science Awards. http://www.ctsaweb.org/ Accessed February 25, 2010). CTSU (Clinical Trial Service Unit & Epidemiological Studies Unit). 2010. Sensible Guidelines for the Conduct of Clinical Trials. http://www.ctsu.ox.ac.uk/projects/sg (accessed Febru- ary 25, 2010). CTTI (Clinical Trials Transformation Initiative). 2009. Clinical Trials Transformation Initia- tive. https://www.trialstransformation.org/ (accessed April 1, 2009). Curt, G. 2009. Step change in safe harbors: Public-private partnerships. The Oncologist 14(4):308–310. Dare, L., and A. Reeler. 2005. Health systems financing: Putting together the “back office.” British Medical Journal 331(7519):759–762. Davis, K. E. 2009. What-if: Back Office Consolidation. http://74.125.95.132/search?q=cache: yOgvCqTeMWsJ:advancingthenonprofit.blogspot.com/2009/10/nonprofit-what-if-back- office.html+%22back+office+consolidation%22&cd=2&hl=en&ct=clnk&gl=us (ac- cessed January 7, 2010). Dilts, D. 2008. CTEP/CIRB Process Flow and Timing Study. Presented at the National Cancer Policy Forum Workshop on Multi-Center Phase III Clinical Trials and NCI Cooperative Groups, July 1, 2008, Washington, DC. Dilts, D. M., and A. B. Sandler. 2006. Invisible barriers to clinical trials: The impact of struc- tural, infrastructural, and procedural barriers to opening oncology clinical trials. Journal of Clinical Oncology 24(28):4545–4552. Dilts, D. M., and A. B. Sandler. 2007. In reply to “Barriers to clinical trials vary according to the type of trial and the institution.” Journal of Clinical Oncology 25(12):1634. 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. Dilts, D. M., A. B. Sandler, S. K. Cheng, J. S. Crites, L. B. Ferranti, A. Y. Wu, S. Finnigan, S. Friedman, M. Mooney, and J. Abrams. 2009. Steps and time to process clinical trials at the Cancer Therapy Evaluation Program. Journal of Clinical Oncology 27(11):1761–1766. Director’s Consumer Liaison Group. 2008. NCI’s Central Institutional Review Board. Presen- tation at the Director’s Consumer Liaison Group Meeting, October 14, 2008. Dodd, L. E., E. L. Korn, B. Freidlin, C. C. Jaffe, L. V. Rubinstein, J. Dancey, and M. M. Mooney. 2008. Blinded independent central review of progression-free survival in phase III clinical trials: Important design element or unnecessary expense? Journal of Clinical Oncology 26(22):3791–3796. DOJ (U.S. Department of Justice). 2008. Response to the CEO Roundtable on Cancer’s Re- quest for Business Review Letter. http://www.justice.gov/atr/public/busreview/237311. htm (accessed December 28, 2009). Doroshow, J. 2008. Restructuring the National Cancer Clinical Trials Enterprise: Institute of Medicine Update. Presented to the Committee on Cancer Clinical Trials and the NCI Cooperative Group Program, December 16, 2008, Washington, DC. Doroshow, J., and Hortobagyi G. N. 2009. Operational Efficiency Working Group Clinical Trials Advisory Committee Report. Bethesda, MD: National Cancer Institute. Dresden, G. M., and M. A. Levitt. 2001. Modifying a standard industry clinical trial consent form improves patient information retention as part of the informed consent process. Academic Emergency Medicine 8(3):246–252.

OCR for page 121
1 OPERATIONS, OVERSIGHT, AND FUNDING Emanuel, E. J., L. E. Schnipper, D. Y. Kamin, J. Levinson, and A. S. Lichter. 2003. The costs of conducting clinical research. Journal of Clinical Oncology 21(22):4145–4150. Epstein, D. 2009. Vision and will: The future of the FDA. The Oncologist 14(4):317–319. Epstein, L. C., and L. Lasagna. 1969. Obtaining informed consent. Form or substance. Ar- chives of Internal Medicine 123(6):682–688. FDA (Food and Drug Administration). 2001. Guidance for Industry: Cancer Drug and Bio- logical Products—Clinical Data in Marketing Applications. http://www.fda.gov/CbER/ gdlns/canclin.htm (accessed April 7, 2009). FDA. 2004. FDA to Establish New Cancer Office and Program: Changes Designed to Improve Efficiency and Consistency of Cancer Product Reviews. http://www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/2004/ucm108326.htm (accessed December 28, 2009). FDA. 2006. Guidance for Industry: Using a Centralized IRB Review Process in Multicenter Clinical Trials. http://www.fda.gov/RegulatoryInformation/Guidances/ucm127004.htm (accessed December 23, 2009). FDA. 2009. U.S. Food and Drug Administration. http://www.fda.gov (accessed December 28, 2009). FNIH (Foundation for the National Institutes of Health). 2009. Foundation for the National Institutes of Health: About Us. http://www.fnih.org/index.php?option=com_content&task= section&id=6&Itemid=37 (accessed December 28, 2009). Glickman, S. W., J. G. McHutchison, E. D. Peterson, C. B. Cairns, R. A. Harrington, R. M. Califf, and K. A. Schulman. 2009. Ethical and scientific implications of the globalization of clinical research. New England Journal of Medicine 360(8):816–823. Gold, J. L., and C. S. Dewa. 2005. Institutional review boards and multisite studies in health services research: Is there a better way? Health Services Research 40(1):291–307. Goldberg, K. B. 2008. New policy on minor changes in trials requires halt in patient enroll- ment. The Cancer Letter 34(16):1–4. Goldberg, K. B. 2009. Advisors approve increase to add new CCOP sites. The Cancer Letter 35(42):6. Grant, B. 2009. The Scientist: NewsBlog: More Regulatory Science: FDA Chief. http://www. the-scientist.com/blog/print/55984/ (accessed December 28, 2009). Greene, S. M., and A. M. Geiger. 2006. A review finds that multicenter studies face substantial challenges but strategies exist to achieve institutional review board approval. Journal of Clinical Epidemiology 59(8):784–790. Grosser, J. M. 2008. Sustaining a Non-Profit in Tough Economic Times. Restructuring: A Possible Solution. Philadelphia, PA: Philadelphia Chamber of Commerce. Hautala, J. 2008. Analysis of Cooperative Group Clinical Trial Costs. Paper presented to the Clinical Trials and Translational Research Advisory Committee, Bethesda, MD. HEW (U.S. Department of Health, Education, and Welfare). 1979. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. http://ohsr.od.nih.gov/guidelines/belmont.html (accessed December 23, 2009). HHS (U.S. Department of Health and Human Services). 1998. Institutional Review Boards: A Time for Reform. Washington, DC: Office of Inspector General, U.S. Department of Health and Human Services. HHS. 2007. Secretary’s Advisory Committee on Human Research Protections (SACHRP). http:// www.hhs.gov/ohrp/sachrp/mtgings/mtg07-07/present.htm (accessed December 28, 2009). HHS. 2009. Office for Human Research Protections (OHRP). http://www.hhs.gov/ohrp/policy (accessed December 28, 2009). ICH (International Conference on Harmonisation). 1996. International Conference on Har- monisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E. http://www.ich.org/LOB/media/MEDIA482.pdf (accessed October 29, 2009).

OCR for page 121
1 A NATIONAL CANCER CLINICAL TRIALS SySTEM Ioannidis, J. P. A., C. D. Mulrow, and S. N. Goodman. 2006. Adverse events: The more you search, the more you find. Annals of Internal Medicine 144(4):298–300. IOM (Institute of Medicine). 2002. Responsible Research: A Systems Approach to Protecting Research Participants. Washington, DC: The National Academies Press. IOM. 2003. Large-Scale Biomedical Research: Exploring Strategies for Future Research. Washington, DC: The National Academies Press. IOM. 2007. Cancer Biomarkers: The Promises and Challenges of Improving Detection and Treatment. Washington, DC: The National Academies Press. IOM. 2008. Improving the Quality of Cancer Clinical Trials: Workshop Summary. Washing- ton, DC: The National Academies Press. IOM. 2009a. Beyond the HIPAA Privacy Rule: Enhancing Privacy, Improving Health Through Research. Washington, DC: The National Academies Press. IOM. 2009b. Breakthrough Business Models: Drug Development for Rare and Neglected Diseases and Individualized Therapies. Workshop summary. Washington, DC: The Na- tional Academies Press. IOM. 2009c. Multi-Center Phase III Clinical Trials and NCI Cooperative Groups: Workshop Summary. Washington, DC: The National Academies Press. Jamrozik, K. 2000. The case for a new system for oversight of research on human subjects. Journal of Medical Ethics 26(5):334–339. Joffe, S., E. F. Cook, P. D. Cleary, J. W. Clark, and J. C. Weeks. 2001. Quality of informed consent in cancer clinical trials: A cross-sectional survey. The Lancet 358(9295):1772–1777. Kaufer, D. S., E. R. Steinberg, and S. D. Toney. 1983. Revising medical consent forms: An empirical model and test. Law, Medicine & Health Care 11(4):155–162. Kinders, R., M. Hollingshead, S. Khin, L. Rubinstein, J. E. Tomaszewski, J. H. Doroshow, R. E. Parchment, and National Cancer Institute Phase 0 Clinical Trials Team. 2008. Preclini - cal modeling of a phase 0 clinical trial: Qualification of a pharmacodynamic assay of poly (ADP-ribose) polymerase in tumor biopsies of mouse xenografts. Clinical Cancer Research 14(21):6877–6885. Kirsch, I., A. Jungeblut, L. Jenkins, and A. Kolstad. 2002. Adult Literacy in America: First Looks at the Result of the National Adult Literacy Survey, 3rd ed. Washington, DC: National Center for Education Statistics, U.S. Department of Education. Kraus, J. R., and J. R. Marjanovic. 1995. Following private-sector lead, Fed to overhaul back office. (Federal Reserve System). American Banker, May 17. http://www.americanbanker. com/issues/160_95/-58613-1.html (accessed February 2, 2010). Kummar, S., R. Kinders, M. E. Gutierrez, L. Rubinstein, R. E. Parchment, L. R. Phillips, J. Ji, A. Monks, J. A. Low, A. Chen, A. J. Murgo, J. Collins, S. M. Steinberg, H. Eliopoulos, V. L. Giranda, G. Gordon, L. Helman, R. Wiltrout, J. E. Tomaszewski, and J. H. Doroshow. 2009. Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in pa- tients with advanced malignancies. Journal of Clinical Oncology 27(16):2586–2588. Kurzrock, R., S. Pilat, M. Bartolazzi, D. Sanders, J. Van Wart Hood, S. D. Tucker, K. Webster, M. A. Mallamaci, S. Strand, E. Babcock, and R. C. Bast, Jr. 2009. Project Zero Delay: A process for accelerating the activation of cancer clinical trials. Journal of Clinical Oncol- ogy 27(26):4433–4440. Lacity, M. C., D. Feeny, and L. P. Willcocks. 2003. Transforming a back-office function: Lessons from BAE Systems’ experience with an enterprise partnership. MIS Quarterly 2(2):86–103. Leith, W. 2002. How to lose a billion. The Guardian, October 26, p. 34. Loh, E. D., and R. E. Meyer. 2004. Medical schools’ attitudes and perceptions regarding the use of central institutional review boards. Academic Medicine 79(7):644–651.

OCR for page 121
1 OPERATIONS, OVERSIGHT, AND FUNDING LoVerde, M. E., A. V. Prochazka, and R. L. Byyny. 1989. Research consent forms: Con- tinued unreadability and increasing length. Journal of General Internal Medicine 4(5):410–412. Mauer, A. M., E. S. Rich, and R. L. Schilsky. 2007. The role of Cooperative Groups in cancer clinical trials. Cancer Treatment and Research 132:111–129. McArthur, M., A. Hodges, A. Wilson, and J. Hautala. 2008. Analysis of Barriers to Accep- tance of NCI Central Institutional Review Board Facilitated Review Process by Institu- tions Conducting NCI-Funded Clinical Trials. Final report. Washington, DC: Science and Technology Policy Institute. McClellan, M., and J. S. Benner. 2009. Four important steps toward 21st century care for patients with cancer. The Oncologist 14(4):313–316. McJoynt, T. A., M. A. Hirzallah, D. V. Satele, J. H. Pitzen, S. R. Alberts, and S. V. Rajkumar. 2009. Building a protocol expressway: The case of Mayo Clinic Cancer Center. Journal of Clinical Oncology 27(23):3855–3860. McKinsey & Company. 2009. “And the winner is . . .” Capturing the Promise of Philanthropic Prizes. New York: McKinsey & Company. McNeil, C. 2005. Central IRBs: Why are some institutions reluctant to sign on? Journal of the National Cancer Institute 97(13):953–955. McWilliams, R., J. Hoover-Fong, A. Hamosh, S. Beck, T. Beaty, and G. Cutting. 2003. Prob- lematic variation in local institutional review of a multicenter genetic epidemiology study. Journal of the American Medical Association 290(3):360–366. MMRC (Multiple Myeloma Research Consortium). 2009. Welcome to the MMRC. http:// www.themmrc.org/ (accessed December 28, 2009). Murphy, S. 2009. Overview of the Consolidation of the Pediatric Oncology Groups. Washing- ton, DC: Committee on Cancer Clinical Trials and the NCI Cooperative Group Program. http://www.iom.edu/~/media/Files/Activity%20Files/Disease/NCPF/2009-Coop-Groups- Study/Murphy_On_the_Merger_of_the_Pediatric_Cancer_Clinical_Trials_Cooperative_ Groups.ashx (accessed March 9, 2010). NCI (National Cancer Institute). 1997. Report of the National Cancer Institute Clinical Tri- als Program Review Group. http://deainfo.nci.nih.gov/ADVISORY/bsa/bsa_program/ bsactprgmin.htm#8a (accessed November 19, 2008). NCI. 2005a. President’s Cancer Panel 200–200 Annual Report: Translating Research into Cancer Care: Delivering on the Promise. Bethesda, MD: National Cancer Institute. NCI. 2005b. Report of the Clinical Trials Working Group of the National Cancer Advisory Board: Restructuring the National Cancer Clinical Trials Enterprise. Bethesda, MD: National Cancer Institute. NCI. 2006. National Cancer Institute Clinical Trials Cooperative Group Program Guidelines. Bethesda, MD: National Cancer Institute. NCI. 2008. Biomarker, Imaging and Quality of Life Studies Funding Program. http://restruc turingtrials.cancer.gov/files/BIQSFP_Announcement_12_12_08.pdf (accessed December 28, 2009). NCI. 2009a. Clinical Trials and Translational Research Advisory Committee Meeting Minutes Menu. http://deainfo.nci.nih.gov/advisory/ctac/ctacminmenu.htm (accessed December 21, 2009). NCI. 2009b. Community Clinical Oncology Program (CCOP). http://prevention.cancer.gov/ programs-resources/programs/ccop/about (accessed December 23, 2009). NCI. 2009c. Division of Extramural Activities: Advisory Boards and Groups. http://deainfo. nci.nih.gov/advisory/boards.htm (accessed December 28, 2009). NCI. 2009d. NCI-Cooperative Group-Industry Relationship Guidelines. http://ctep.cancer. gov/industryCollaborations2/guidelines.htm (accessed December 28, 2009).

OCR for page 121
1 A NATIONAL CANCER CLINICAL TRIALS SySTEM NCI. 2009e. NCI Trial Complexity Elements & Scoring Model (Version 1.2). http://ctep. cancer.gov/protocoldevelopment/docs/trial_complexity_elements_scoring.doc (accessed October 20, 2009). NCI. 2009f. Restructuring the NCI Clinical Trials Enterprise. http://restructuringtrials.cancer. gov/steering/overview (accessed December 21, 2009). Niederhuber, J. E. 2009. Facilitating patient-centered cancer research and a new era of drug discovery. The Oncologist 14(4):311–312. NIH (National Institutes of Health). 2009. Public Private Partnership Program. http://ppp. od.nih.gov/ (accessed November 4, 2009). Nosowsky, R., and T. J. Giordano. 2006. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule: Implications for clinical research. Annual Review of Medicine 57(1):575–590. OHRP (Office for Human Research Protections). 2009. Advanced notice of proposed rulemak- ing; requests for public comment. Federal Register 74(42):9578–9583. OHRP, NIH (National Institutes of Health), AAMC (American Association of Medical Col- leges), and ASCO (American Society of Clinical Oncology). 2005. Alternative Mod- els of IRB Review: Workshop Summary Report. http://www.dhhs.gov/ohrp/sachrp/ documents/AltModIRB.pdf (accessed April 7, 2009). Paasche-Orlow, M. K., H. A. Taylor, and F. L. Brancati. 2003. Readability standards for informed-consent forms as compared with actual readability. New England Journal of Medicine 348(8):721–726. PCAST (President’s Council of Advisors on Science and Technology). 2008a. Priorities for Personalized Medicine. Washington, DC: Office of Science and Technology Policy. PCAST. 2008b. University-Private Sector Research Partnerships in the Innovation Ecosystem. Washington, DC: Office of Science and Technology Policy. Reaman, G. 2009. Children’s Oncology Group: A National/International Infrastructure for Pediatric Cancer Clinical Translational Research. Presentation to the Institute of Medi- cine Committee on Cancer Clinical Trials and the NCI Cooperative Group Program, April 23, 2009, Washington, DC. Rhoades, S. A. 1998. The efficiency effects of bank mergers: An overview of case studies of nine mergers. Journal of Banking & Finance 22(3):273–291. Ridpath, J. R., S. M. Greene, and C. J. Wiese. 2007. PRISM Readability Toolkit, 3rd ed. Seattle, WA: Group Health Center for Health Studies. RTI International. 2007. Evaluation of the NCI Central Institutional Review Board to Im- prove Cancer Clinical Trials System; CIRB User Satisfaction Survey Research. Final report. Research Triangle Park, NC: RTI International. SACHRP (Secretary’s Advisory Committee on Human Research Protections). 2005. Sum- mary of SACHRP’s Recommendations on the HIPAA Privacy Rule. Washington, DC: Secretary’s Advisory Committee on Human Research Protections. SACHRP. 2008. Letter to HHS Secretary, September 18. Secretary’s Advisory Committee on Human Research Protections, Washington, DC. Schilsky, R. L., J. Abrams, J. Woodcock, G. Fyfe, and R. Erwin. 2008. Data Submissions Standards and Evidence Requirements, Conference on Clinical Cancer Research, Panel 1. Washington, DC: Brookings Institution, Engelberg Center for Health Care Reform. Schroen, A. T., G. R. Petroni, H. Wang, B. Djulbegovic, C. L. Slingluff, X. F. Wang, R. Gray, D. J. Sargent, W. Cronin, and J. Benedetti. 2009. Challenges to accrual predictions to phase III cancer clinical trials: A survey of study chairs and lead statisticians of 248 NCI- sponsored trials. Journal of Clinical Oncology 27:15s (suppl; abstr 6562). Sharp, S. M. 2004. Consent documents for oncology trials: Does anybody read these things? American Journal of Clinical Oncology 27(6):570–575.

OCR for page 121
1 OPERATIONS, OVERSIGHT, AND FUNDING Shortell, S. M., T. M. Waters, K. W. B. Clarke, and P. P. Budetti. 1998. Physicians as double agents: Maintaining trust in an era of multiple accountabilities Journal of the American Medical Association 280(12):1102–1108. Steensma, D. P. 2009. The ordinary miracle of cancer clinical trials. Journal of Clinical Oncol- ogy 27(11):1737–1739. Sudore, R. L., C. S. Landefeld, B. A. Williams, D. E. Barnes, K. Lindquist, and D. Schillinger. 2006. Use of a modified informed consent process among vulnerable patients: A descrip- tive study. Journal of General Internal Medicine 21(8):867–873. Taheri, P. A., D. Butz, L. C. Griffes, D. R. Morlock, and L. J. Greenfield. 2000. Physician impact on the total cost of care. Annals of Surgery 231(3):432–435. Tait, A. R., T. Voepel-Lewis, S. Malviya, and S. J. Philipson. 2005. Improving the readability and processability of a pediatric informed consent document: Effects on parents’ under- standing. Archives of Pediatric and Adolescent Medicine 159(4):347–352. Tarnowski, K. J., D. M. Allen, C. Mayhall, and P. A. Kelly. 1990. Readability of pediatric biomedical research informed consent forms. Pediatrics 85(1):58–62. Tufts University. 2009. Tufts Center for the Study of Drug Development. http://csdd.tufts. edu/Default.asp (accessed April 1, 2009). Tully, J., N. Ninis, R. Booy, and R. Viner. 2000. The new system of review by multicentre research ethics committees: Prospective study. British Medical Journal 320:1179–1182. Wagner, T., C. Murray, J. Goldberg, J. Adler, and J. Abrams. October 19, 2009, posting date. Costs and benefits of the National Cancer Institutional Review Board. Journal of Clinical Oncology Epub ahead of print. Waldinger, M. 2008. Cost Out. Presented at the National Cancer Policy Forum Workshop on Multi-Center Phase III Clinical Trials and NCI Cooperative Groups, July 2, 2008, Washington, DC. Wechsler, J. 2007. Central vs. local: Rethinking IRBs. Applied Clinical Trials Online (February 1, 2007). http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/article/ articleDetail.jsp?id=401619 (accessed April 7, 2009). Wickerham, L. 2009. A “Modest Proposal” and a Few Suggestions Concerning Cooperative Group Clinical Trials. Presented to the Committee on Cancer Clinical Trials and the NCI Cooperative Group Program, April 23, 2009, Washington, DC. Woodcock, J., and R. Woosley. 2008. The FDA critical path initiative and its influence on new drug development. Annual Review of Medicine 59(1):1–12. Yang, S. X., S. Kummar, S. M. Steinberg, A. J. Murgo, M. Gutierrez, L. Rubinstein, D. Nguyen, G. Kaur, A. P. Chen, V. L. Giranda, J. E. Tomaszewski, J. H. Doroshow, and The National Cancer Institute Phase 0 Working Group. 2009. Immunohistochemical detec- tion of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas. Cancer Biology and Therapy 8(21):2004–2009. Young, D. R., D. T. Hooker, and F. E. Freeberg. 1990. Informed consent documents: increasing comprehension by reducing reading level. IRB: a Review of Human Subjects Research 12(3):1–5. Yusuf, S., J. Bosch, P. J. Devereaux, R. Collins, C. Baigent, C. Granger, R. Califf, and R. Temple. 2008. Sensible guidelines for the conduct of large randomized trials. Clinical Trials 5(1):38–39.

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