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Currently Skimming:

Overview of Conclusions and Recommendations
Pages 5-40

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From page 5...
... and are critical to progress in cancer treatment. Publicly funded clinical trials also play a vital role and are complimentary to industry trials in advancing science and patient care, particularly by addressing questions that are important to patients but are less likely to be top priorities of industry.
From page 6...
... , which comprises 10 Groups that involve more than 3,100 institutions and 14,000 investigators who enroll more than 25,000 patients in clinical trials each year. Most Cooperative Group trials are either moderate-scale Phase II or large-scale Phase III clinical trials that may have practice-changing implications directly relevant to patient care.
From page 7...
... conduct a consensus study of cancer clinical trials and the Clinical Trials Cooperative Group Program and develop recommendations for how to improve the current system. To address the charge, the IOM appointed a 17-member committee with a broad range of expertise and experience, including experts in biomedical and clinical investigations in academia and community practice, statistics, radiology, research and development in the biotechnology and pharmaceutical industries, management research, systems engineering, the health insurance industry, and patient advocacy.
From page 8...
... Multi-institutional collaborations are necessary to conduct large Phase III trials for indications such as adjuvant therapy, first-line therapy of metastatic disease, and prevention; single institutions are not capable of undertaking such large-scale trials. For research on some other diseases, the National Institutes of Health (NIH)
From page 9...
... Given its long and impressive history of accomplishment, the Cooperative Group Program should ideally provide an established infrastructure for the rapid and efficient translation of scientific knowledge into practical therapeutic solutions that incorporate targeted agents matched to the characteristics of the patient and tumor and routinely achieve change in clinical practice, as well as FDA approval, where appropriate. However, although a strong and adequately funded clinical trials coop
From page 10...
... Novel, multidisciplinary solutions are needed for currently intractable problems in cancer clinical trials. Redesigning a more effective and efficient clinical trials system would likely speed the pace of advances in cancer patient care.
From page 11...
... Incorporate innovative science and trial design into cancer clinical trials   5.  Support and use biorepositories   6.  Develop and evaluate novel trial designs   7.  Develop standards for new technologies Goal III. Improve prioritization, selection, support, and completion of cancer clinical trials   8.  Reevaluate the role of NCI in the clinical trials system    9.  Increase the accrual volume, diversity, and speed of clinical trials 10.  Increase funding for the Cooperative Group Program Goal IV.
From page 12...
... Thus, meaningful change to the cancer clinical trials system will require actions by the numerous stakeholders. Although NCI should play a leading role in instituting the necessary changes, other agencies within the U.S.
From page 13...
... (b) Overview of the proposed structure and function of the Cancer Clinical Trials Cooperative Group Program, as described in the committee's recommendations.
From page 14...
... Review by NCI Asynchronous Peer Review of FDA Cooperative Groups NCI Local IRB Patient enrollment at participating trial sites (approved by a specif ic Group) NCI CIRB Data NCI Oversight and Support Data Management Data Analysis Publication Figure O-1a R01707
From page 15...
... B Cooperative Group A (Repeat for each Group) Multidisciplinary Statistical Off ices Disease Site Committees Funding Concurrent New Data Analysis Publication Peer Review of Performance Propose Trial Concepts Front Off ice Metrics Prioritization and Selection via Peer Review Local IRB Funding Consolidated High-priority Clinical Trial Protocols Back Off ice Peer Review with Full Funding from NCI Operations of Back and Data NCI Off ice New FDA Management CIRB Operations Performance Patient enrollment at any trial site Functions Metrics NCI certif ied to participate in a Support National Trials Network Data 1
From page 16...
... key planning and scientific evaluations should be at the disease site • committee level. The focus should be on the quality and success of the clinical trial concepts developed and the committee's record of development of new investigators.
From page 17...
... Such a system would ideally maintain strong competition for trial concepts among a smaller number of Cooperative Groups and their disease site committees and thus help to ensure that only the highest-priority trials are undertaken. A reduction in the number of trials competing for patient enrollment would help to align patient and clinician incentives, as providers would focus on finding the best possible trial for each patient and his/her particular disease, regardless of where the trial originated.
From page 18...
... Although good clinical practice guidelines provide an international ethical and scientific quality standard for the design, conduct, recording, and reporting of the findings of clinical trials that involve the participation of human subjects, at present there is no mechanism for the systematic collection of best management and administrative practices that can be used as benchmarks by a clinical trials office in a cancer center or a Cooperative Group. Furthermore, few standard processes or metrics of what constitutes operational "quality" in the development or management of clinical trials exist.
From page 19...
... Department of Health and Human Services should lead a transagency effort to streamline and harmo nize government oversight and regulation of cancer clinical trials. For example, All review bodies should distinguish between major review con • cerns (regarding patient safety and critical scientific flaws, which must be addressed)
From page 20...
... Multiple agencies and institutional bodies of HHS review and provide oversight for cancer clinical trials, including NCI, FDA, the Office for Human Research Protections (OHRP) , the Office for Civil Rights (OCR)
From page 21...
... Eliminating unnecessary and onerous data requirements would also conserve resources and result in the testing of more combination therapies in particular. A major challenge unique to large multi-institutional studies is the involvement of many local IRBs.
From page 22...
... Rationale Cancer clinical trials often necessitate effective collaboration among diverse stakeholders, but there are numerous challenges to achieving such collaborations. For example, negotiations to reach contract and licensing agreements to transfer or share materials, data, and intellectual property (IP)
From page 23...
... However, novel hybrid funding mechanisms, as well as new efforts to establish publicprivate 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. Maintaining 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.
From page 24...
... GOAL II. INCORPORATE INNOvATIvE SCIENCE AND TRIAL DESIGN INTO CANCER CLINICAL TRIALS background Progress in the treatment of cancer patients depends on the effective incorporation of scientific advances into clinical trials.
From page 25...
... The increasing complexity of cancer clinical trials, along with the great expense and high failure rate of late-stage clinical trials, has spurred innovation in trial design as well, with the aim of conducting clinical trials more efficiently and with a greater likelihood of success. However, when new methods or technologies are incorporated into clinical trials, standards to ensure that the results collected at the various trial sites are consistent enough to attain accurate and meaningful conclusions from a study are often lacking.
From page 26...
... The creation of a national inventory of samples held by the Cooperative Groups would also greatly facilitate important research in correlative science. Recommendation 6: Cooperative Groups should lead the development and assessment of innovative designs for clinical trials that evalu ate cancer therapeutics and biomarkers (including combinations of therapies)
From page 27...
... For example, prospective clinical trial designs that randomize patients on the basis of biomarkers or treatments, or both, should be explored and evaluated. For targeted therapies, a predictive hypothesis for a biomarker should be put forward in the preclinical phase and tested in early-phase clinical trials (Phase I and II trials)
From page 28...
... The consistent development of standard methodologies for established tumor-imaging modalities (e.g., computed tomography, fluorodeoxyglucose positron emission tomography, and conventional magnetic resonance imaging) by expert panels, along with a requirement that manufacturers meet those standards, could significantly improve the accuracy and value of those tests.
From page 29...
... The process of conducting large-scale trials has become highly complex, with the incorporation of new technologies and trial designs, the increasing number of therapeutic agents to be tested, the increase in the number of Cooperative Groups, and the evolving regulatory environment. Many of these issues are addressed in the recommendations in the preceding sections, but it is also necessary to examine the contributions of and interactions between NCI and the Cooperative Groups in developing and implementing large-scale cancer clinical trials.
From page 30...
... Despite this decrease in funding, the Cooperative Group Program has maintained patient accrual, with several hundred clinical trials ongoing at any given point. This level of funding, which represents approximately 3 percent of the total NCI budget, is simply not sufficient to support the number of trials that the Groups undertake.
From page 31...
... NCI has crucial responsibilities in the clinical trials system, for example, by providing a framework for both cooperatively and competitively organized interactions between Groups and their committees and in the management of IND sponsorship. As already noted in Recommendation 2, there are numerous steps that NCI could take to further improve the support and facilitation of high-priority trials.
From page 32...
... For example, they should develop electronic tools that cue physicians practicing oncology via • electronic medical record systems about trials for which a particu lar patient is eligible; encourage patient eligibility criteria that allow the broadest partici • pation possible; encourage greater enrollment in high-priority trials, regardless of • where the trial originates; establish a centralized credentialing system for participating sites; • eliminate investigators and sites with low rates of accrual or inad • equate data management skills or quality; strive to make participation in clinical trials a key component of • clinical practice and to achieve the exemplary attributes of the American Society of Clinical Oncology for academic and commu nity clinical trial sites, including high accrual rates4 of 10 percent or more; and encourage greater participation of patient advocates in trial con • cept development and accrual planning, and partnerships with patient advocacy organizations to support accrual efforts. 4 The American Society of Clinical Oncology defines "accrual rate" as the number of patients enrolled in trials annually/number of new patients seen annually.
From page 33...
... Some public databases with information about clinical trials exist, but in their current form, they may not adequately serve the information needs of physicians and patients as they are not part of the normal work flow of a busy clinical practice. User-friendly electronic tools, available with the right features for a physician's work flow, would increase awareness of trials and make it easier for physicians and patients to enroll in the most appropriate studies.
From page 34...
... 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. Rationale High-priority trials must be adequately funded to efficiently and effectively attain results that can move the field forward.
From page 35...
... Biomedical imaging and other biomarker tests are commonly becoming integral components of modern cancer clinical trials, but supplemental funding for these tests must be obtained by the Cooperative Groups through other support mechanisms. 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.
From page 36...
... Even if patients are eligible for trials and are informed about the option by their physicians (as discussed in the section describing Goal III) , they may decline because of financial concerns, as coverage of patient care costs in clinical trials by health insurers is not consistent.
From page 37...
... Ultimately, the inability to recruit, train, and retain a sufficient number of talented clinical investigators will compromise the ability to conduct clinical trials in the United States, to the detriment of the U.S. biomedical research enterprise and to patients, those who participate in clinical trials as well as those who do not.
From page 38...
... 3590) was signed into law by President Barack Obama on March 23, 2010, which provides coverage of routine care costs for individuals participating in approved clinical trials.
From page 39...
... For physicians, even in cases in which routine patient care in a clinical trial is covered by health insurers, the current payment policies do not reflect the additional time needed to enroll and follow patients in a trial. For example, if a patient receiving off-protocol chemotherapy reports an adverse event or unanticipated problem, the physician can respond however he or she thinks is clinically the most appropriate.
From page 40...
... The committee envisions a system that retains the current strengths, but moves beyond collaboration to integration, with reorganized structures and operations in a truly national clinical trials network and with sufficient funding and support to enable the rapid completion of well-designed, high-priority cancer clinical trials that advance patient care.


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