4
Physician and Patient Participation in Cancer Clinical Trials

The ability to translate scientific discoveries into clinical advances relies on a robust clinical trials infrastructure, which is largely dependent on a critical mass of patients and physicians willing to participate in clinical trials. However, current indications suggest that participation in clinical trials is the exception rather than the rule both for patients and for physicians. It is estimated that only 3 percent of adults with cancer participate in clinical trials, and people who are members of racial and ethnic minorities, elderly and low-income individuals, and people who live in rural areas remain underrepresented (EDICT, 2008). Without adequate rates of participation by patients and physicians, it is unlikely that important research questions with the potential to improve patient outcomes will be answered efficiently and effectively. Furthermore, the trend toward targeted therapy and personalized medicine necessitates larger numbers of patients willing to participate in clinical trials, since these trials are increasingly reliant on stratified populations. According to the National Cancer Institute (NCI), the true effectiveness of cancer therapies will not be known unless more people are involved in clinical trials (NCI, 2001).

The committee concluded that the value of clinical trials in advancing patient care necessitates a paradigm change in the current approach to clinical trials. Building on discussions at a prior Institute of Medicine (IOM) workshop (IOM, 2009b), the committee emphasized that the therapies offered through clinical trials should ideally be considered the preferred treatment choice for physicians and patients, if they are available. Broad participation in a publicly sponsored clinical trials system—by investigators, community physicians, cancer centers, and patients—will enhance the system’s impact by efficiently providing practice-changing evidence.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 191
4 Physician and Patient Participation in Cancer Clinical Trials The ability to translate scientific discoveries into clinical advances relies on a robust clinical trials infrastructure, which is largely dependent on a critical mass of patients and physicians willing to participate in clinical trials. However, current indications suggest that participation in clinical trials is the exception rather than the rule both for patients and for physi- cians. It is estimated that only 3 percent of adults with cancer participate in clinical trials, and people who are members of racial and ethnic minori- ties, elderly and low-income individuals, and people who live in rural areas remain underrepresented (EDICT, 2008). Without adequate rates of par- ticipation by patients and physicians, it is unlikely that important research questions with the potential to improve patient outcomes will be answered efficiently and effectively. Furthermore, the trend toward targeted therapy and personalized medicine necessitates larger numbers of patients willing to participate in clinical trials, since these trials are increasingly reliant on stratified populations. According to the National Cancer Institute (NCI), the true effectiveness of cancer therapies will not be known unless more people are involved in clinical trials (NCI, 2001). The committee concluded that the value of clinical trials in advancing patient care necessitates a paradigm change in the current approach to clini- cal trials. Building on discussions at a prior Institute of Medicine (IOM) workshop (IOM, 2009b), the committee emphasized that the therapies offered through clinical trials should ideally be considered the preferred treatment choice for physicians and patients, if they are available. Broad participation in a publicly sponsored clinical trials system—by investiga- tors, community physicians, cancer centers, and patients—will enhance the system’s impact by efficiently providing practice-changing evidence. 11

OCR for page 191
12 A NATIONAL CANCER CLINICAL TRIALS SySTEM Although many important clinical trials are undertaken by the pharma- ceutical industry, relying solely on pharmaceutical companies and contract research organizations to maintain a clinical trials infrastructure would be detrimental for a variety of reasons. First, companies are primarily responsi- ble to their shareholders and have less incentive to conduct certain types of clinical trials that are in the best interests of society. An industry-only clini- cal trials infrastructure may neglect important areas of research, including research on the comparative effectiveness of different therapeutics, research on novel indications for older drugs, determination of dose intensity, the development of combination products from multiple companies, research on the development of drugs for the treatment of rare diseases, evaluation of different surgical and radiation treatment methods, research on screening and prevention strategies, and research on rehabilitation and quality of life following therapy. In addition, industry trials are increasingly moving away from the United States (Agres, 2005; Glickman et al., 2009; IOM, 2009b; Normile, 2008), which could lower U.S. patient access to clinical trials and, in some instances, lower the applicability of the findings of clinical trials to the U.S. population. This movement of clinical trials overseas threatens the capacity of the United States to maintain a clinical trials infrastructure and workforce. Academic centers and community practices play a crucial role in training and mentoring the next generation of clinical investigators, but recent evidence suggests that the number of U.S.-based principal investiga- tors is declining (Getz, 2007), potentially shrinking the training pipeline for new clinical investigators and negatively affecting the U.S. economy. Rather than rely on a pharmaceutical industry-centered clinical trials infrastructure, the committee concluded that incentives must be realigned so that clinical investigators and patients will choose to participate in a publicly sponsored clinical trials system. The committee took a broad view of the disincentives preventing high rates of participation. For clinical investigators, the committee emphasized issues related to reimbursement, extensive regulatory burdens, and academic procedures related to tenure, promotion, and career development. For patients, the committee discussed third-party coverage for participation in clinical trials and patient and phy- sician attitudes about participation in clinical trials, including knowledge of the availability of clinical trials. Many of these issues have been addressed in prior evaluations of the Clinical Trials Cooperative Group Program (NCI, 1997, 2005b), but low rates of participation in cancer clinical trials remains a significant barrier to the efficient translation of scientific discover- ies into advances in patient care. CLINICAL INvESTIGATOR PARTICIPATION Retaining a workforce competent in conducting clinical trials is essen- tial to maintaining a strong publicly funded clinical trials infrastructure.

OCR for page 191
1 PHySICIAN AND PATIENT PARTICIPATION However, the current system does not foster clinical investigator participa- tion in publicly sponsored clinical trials. Misaligned incentives, both in aca- demia and in physician practices, inhibit robust participation. Realigning incentives for clinical investigators so that they may participate in clinical trials is essential to increasing patient accrual. Physicians who participate in Cooperative Group trials do so despite significant barriers and disincentives and have been referred to as an “all- volunteer army” because the costs of conducting trials outstrip the reim- bursements provided by the NCI (IOM, 2009b; see also Chapter 3). Many of the reasons that investigators continue to participate in trials include the desire to advance cancer research and improve future patient care, to be involved in the design and conduct of clinical trials, and to offer patients access to state-of-the-art care, including access to investigational compounds. Despite the importance of cancer clinical trials, the disincentives limit- ing provider participation are numerous. The American Cancer Society Cancer Action Network (ACS CAN) breaks down the disincentives into financial barriers, regulatory burdens, awareness of clinical trial options, and physician perceptions of clinical trials (ACS CAN, 2009). In addition to the barriers that are common to all investigators, academic physicians and community physicians confront somewhat unique barriers. Clinical trial involvement is not well rewarded in tenure and promotion processes in academia and is not aligned with the time investment required for con- ducting large, multi-institutional trials. Community practitioners lack the needed infrastructure and support to actively participate in clinical trials. Financial and Regulatory barriers Participating Sites In 2009, the American Society of Clinical Oncology (ASCO) con- ducted an Internet poll of Cooperative Group sites seeking to understand whether financial or other barriers are preventing participation in Coopera- tive Group clinical trials. The survey found that 32 percent of respondents (155 of 478 sites)1 indicated that they plan on limiting participation2 in the Cooperative Group Program (Blayney, 2009). Seventy-five percent of survey respondents who indicated that they were limiting participation cited 1 A limitation of the interpretation of these findings is that the number of sites that received the poll is unknown, and it is unclear whether the 478 respondents are representative of the estimated 1,800 sites involved in Cooperative Group research. 2 The survey defined limited participation as (1) a cap on the number of patients to be accrued, (2) a limit on the number of trials offered, or (3) a limit to the number of Coopera- tive Group affiliations.

OCR for page 191
1 A NATIONAL CANCER CLINICAL TRIALS SySTEM inadequate per case reimbursement as an important factor in this decision. An additional 38 sites (or 8 percent or those surveyed) were considering these limitations. Although many respondents indicated a preference for participation in Cooperative Group trials, 49 respondents indicated that their sites were increasing their rate of participation in industry trials. Jeffrey Abrams, associate director of the Cancer Therapy Evaluation Pro- gram, has also noted that cancer centers are curtailing their participation in Cooperative Group trials. In a recent IOM workshop, Abrams said some cancer centers have capped the number of accruals that can go to Coopera- tive Group trials, because they believe that it is too much of an economic burden (IOM, 2009b). As the findings of the survey suggest, cancer centers and other sites enrolling patients in Cooperative Group clinical trials may be limiting participation because of inadequate reimbursement. Although Cooperative Group trials are recognized for their fundamental importance in setting the standard of care, institutions are faced with increasing cost restraints, making it difficult to participate in inadequately reimbursed activities, such as Cooperative Group trials. Despite the resource-intensive nature of clini- cal trials, the per patient reimbursement of $2,000 has remained the same since 1999 (IOM, 2009b). In June 2008, the NCI began using a complex- ity rating scheme to increase the rate of reimbursement for complex clini- cal trials, with the maximum reimbursement of $3,000 (Mooney, 2008). However, the extra $1,000 of reimbursement for complex clinical trials is still far below estimated costs required to conduct clinical trials, which in 2004 were estimated to be a median cost of $3,500 and $6,000 per patient for Phase III and Phase II trials, respectively (C-Change, 2005). For many cancer clinical trials, this amount appears to be inadequate to cover most labor costs, per subject enrollment costs, and additional research-related paperwork and reporting requirements (ACS CAN, 2009). If an academic medical center or a physician practice stands to lose thousands of dollars per patient by participating in the current publicly sponsored clinical trials system, it is not surprising that physician preferences are to treat patients with the standard of care or with a therapeutic agent off protocol, rather than being involved in a significantly more costly and more burdensome clinical trial. Individual Physicians According to one survey, only 13 percent of physicians are clinical investigators (Taylor, 2004). Aside from the lack of opportunity to par- ticipate as a clinical investigator, that survey found that the primary rea- sons for not acting as a clinical investigator include the time commitment involved (32 percent), a lack of personal support (30 percent), not having

OCR for page 191
1 PHySICIAN AND PATIENT PARTICIPATION the resources to run a successful trial (26 percent), and the paperwork bur- den (24 percent). However, only 17 percent of physicians surveyed said that they had no interest in becoming a clinical investigator (Taylor, 2004). Physicians who enroll patients in Cooperative Group clinical trials face increased time and effort not reflected in current reimbursement policies. To participate in clinical trials, physicians must find applicable trials for their patients, explain these trials to their patients, and obtain informed consent, which can add significant time and effort to a physician’s workload (Comis et al., 2003). On average, 4 hours of a physician’s time is required before a patient can be enrolled in a trial, and some of that time is devoted to patients who ultimately choose not to participate in the clinical trial (Mansour, 1994). If a patient enrolls in a trial, the data collection and documentation requirements are substantially more onerous for patients in a trial than for patients receiving standard therapy outside of a trial (Comis et al., 2003). The complexity of the protocol, the recruitment and selection of study participants, high-intensity visit schedules, protocols that deviate from the standard of care, and the complexity and acuity of the patient population all add to the costs of treating patients within a clini- cal trial setting (ACS CAN, 2009). At an IOM workshop, one community physician noted that he gives double bookings for patients participating in complex clinical trials (for example, one with two targeted molecules) to have time to sort through all of the toxicities and to adjust the doses for each drug (IOM, 2009b). In addition, radiologists and pathologists must spend additional time conducting tests and analyses for clinical trials and resist doing so because they are not compensated for the extra work and time required. As discussed in Chapter 3, the regulatory requirements for clinical trials are highly complex. These requirements can also prevent robust pro- vider participation. Clinical investigators must contend with ambiguous and complex regulations in clinical trials, including the reporting require- ments of the Food and Drug Administration (FDA), in addition to those of the National Institutes of Health (NIH), such as requirements for proof of adherence to good clinical practice guidelines and human subject pro- tections; reporting of adverse events; and adherence to data monitoring, audits, and quality control requirements (ACS CAN, 2009). Oncologists are less likely to refer patients for participation in a clinical trial if they perceive the paperwork to be onerous and trial entry requirements to be too stringent (Siminoff et al., 2000). Given the low reimbursement levels and the voluntary nature of the Cooperative Group Program, the added burden of the regulatory requirements on clinical investigators is a major disincentive to participation. In light of the additional time and resources required for physician participation in a clinical trial, the committee recognized the importance

OCR for page 191
1 A NATIONAL CANCER CLINICAL TRIALS SySTEM of establishing a mechanism to reimburse physicians for their time com- mensurate with the level of work involved with participation in a trial. Specifically, the committee recommends that NCI increase the per case reimbursement rate. The committee also recommends that the American Medical Association establish new Current Procedural Terminology codes (CPT codes), reimbursed by the Centers for Medicare & Medicaid Services (CMS), private insurers, and other third-party payors, to pay an enhanced reimbursement for offering, enrolling, managing, and following a patient in a clinical trial. New CPT codes, with a higher reimbursement rate, that acknowledge the additional time and resources needed to counsel and care for a patient in a clinical trial would address an important deterrent to physician participation in clinical trials. With a proper definition of eligible trials, use of such a code could be easily audited. The committee also discussed the importance of funding principal investigators who participate in Cooperative Group research. The commit- tee distinguished two types of principal investigators: first, principal inves- tigators who develop and oversee a Cooperative Group clinical trial, and second, principal investigators who oversee all Cooperative Group trials at a participating institution. Both of these types of principal investigators are important to the design, implementation, and monitoring of Coopera- tive Group trials. Therefore, the committee recommends that NCI provide funding to site and trial principal investigators to cover the time they need to develop and oversee approved clinical trials. In a similar step, the Opera- tional Efficiency Working Group recommended that NCI officially recog- nize investigators for leadership in the design and conduct of Cooperative Group trials (Doroshow and Hortobagyi, 2009). Participation by Community Physicians The majority of cancer patients are treated in community settings, whereas the majority of cancer patients who enroll in clinical trials are treated within academic settings (Cox and McGarry, 2003; Somkin et al., 2005). However, community physicians also play a vital role in recruiting patients into clinical trials, especially large-scale trials of methods for cancer screening, adjuvant therapies, and first-line therapies for metastatic disease. One of the strengths of the Cooperative Group Program is the extensive involvement of physicians and patients in community practices. Participa- tion by physicians and patients within community settings helps to ensure that the results of clinical trials are meaningful to a broad segment of the U.S. population and provides the patients with access to promising, innova- tive therapies as they are developed. NCI’s Cooperative Group Program is responsible for enrolling 85 percent of patients who enter NCI-sponsored trials, and about 65 percent of these patients enter from community-based

OCR for page 191
1 PHySICIAN AND PATIENT PARTICIPATION practices that include Community Clinical Oncology Program and aca- demic medical center affiliates (C-Change and Coalition of Cancer Cooper- ative Groups, 2006). Despite the importance of enrolling community-based patients into clinical trials, a number of barriers prevent more community physicians from participating in clinical trials. During the IOM workshop on multicenter clinical trials, one speaker noted that doctors have virtually no incentives to enroll patients in a clinical trial but have many disincen- tives (IOM, 2009b). As with all physicians, financial burdens, regulatory complexity, awareness of trial availability, and attitudes about participa- tion are barriers to clinical trial participation for community physicians. However, physicians in community practices may have fewer resources to support participation in a clinical trial, including a lack of logistical support and a lack of clinical research nurses. Some modest resources are available to support community practitioners, such as the Community Oncology Research grant, which gives up to $30,000 to support three community- based practices that enhance their clinical trials programs (ASCO, 2008). Despite the availability of these support mechanisms, a large discrepancy between the per case reimbursement and the actual cost of participation remains, and this is a major disincentive to participation. As mentioned above, a primary mechanism for improving community physician involve- ment in clinical trials includes better reimbursement for physicians enrolling patients in clinical trials. In addition, the committee emphasized the importance of recognizing the research staff who participate in cancer clinical trials, including physi- cians, nurses, clinical research associates, pharmacists, and others who conduct clinical trials. The committee recommends that NCI work with a nonprofit foundation to develop a certification program, as recommended by the Clinical Trials Working Group (CTWG). Such a program could be one component of site credentialing for participation in Cooperative Group trials (see also the section on participation patterns). A certification program could distinguish investigators who actively participate in clinical trials and have met other metrics of high-quality care. Patients may seek out certified physicians, encouraging physicians to become certified and become more involved in clinical trials. Singling out investigators who participate in clinical trials is consistent with the perspective that well-designed, properly implemented clinical trials are the optimal treatment option. In well-designed trials, patients randomized to the control group typically receive the current standard of care, whereas those allocated to the new treatment receive a treatment hypothesized to be similar to or better than the standard of care (Ellis, 2000). In one survey of oncology leaders at community integrated health centers, eight leaders agreed that trial participation is imperative to high-quality care, whereas only one leader did not support that assessment (Somkin et al., 2005).

OCR for page 191
1 A NATIONAL CANCER CLINICAL TRIALS SySTEM Several analyses have attempted to assess whether clinical trial participants have better outcomes than nonparticipants, with mixed results (Braunholtz et al., 2001; Davis et al., 1985; Peppercorn et al., 2004; Robinson et al., 2009; Roy et al., 2000; Stiller, 1994). Although some studies suggest that individuals who participate in clinical trials have better outcomes than non- participants in specific medical areas, systematic reviews looking at clinical trials overall have not found such an effect. But these reviews did show that patients participating in a randomized controlled trial did not have worse outcomes than those receiving a similar treatment outside the trial (Vist et al., 2005, 2008). The National Comprehensive Cancer Network (NCCN) guidelines also state that “NCCN believes that the best management of any cancer patient is in a clinical trial” (NCCN, 2009). Quality improvement programs, such as the ASCO Quality Oncology Practice Initiative (QOPI), may also single out high-performing practicing oncologists to patients and other stakeholders. QOPI is a voluntary self- assessment program that certifies oncology practices for high-quality care. ASCO analyzes practice data for evidence-based quality measures and provides feedback to practices to identify areas of improvement (ASCO certification program emphasizes quality of care, 2009). For example, QOPI could use a metric to assess how many of a physician’s patients are enrolled in clinical trials. Currently, Kaiser Permanente uses trial enrollment as a quality metric as part of its practice-based accountabilities (Wallace, 2009). Participation by Academic Clinicians Tenure and promotion policies and declining numbers of clinical inves- tigators may prevent higher levels of involvement by academic investigators in clinical research. Tenure and promotion policies tend to value individual investigator-initiated, basic research more than multi-institutional, team- oriented clinical research. In addition, the shrinking physician scientist pipeline suggests that additional efforts may be needed to encourage, train, and retain clinical investigators. Recognizing and Rewarding Clinical and Team Research Clinical investigators require a specialized skills set, training, and ori- entation to be successful. They must be able to navigate the complex regu- latory environment, work in teams, share the rewards of their work, and defer financial compensation while spending years in training (Andrews et al., 2009). Despite these unique skills and orientation, physician scientists focused on clinical research may not receive academic recognition and advancement commensurate with the value of their work. This may be due

OCR for page 191
1 PHySICIAN AND PATIENT PARTICIPATION to a number of factors, including a lack of awareness by promotions com- mittees of what such research entails; the collaborative nature of research, which makes it difficult to mark individual accomplishments; the time span needed to obtain results from clinical research; and the underfunding of the Cooperative Groups (IOM, 2009b). Because Cooperative Group research is primarily accomplished in multi-institutional settings, promotion commit- tees may be unaware of the intellectual rigor and complexity involved in trial design and protocol implementation. Likewise, promotion committees may not have a sense of the time commitment required for clinical trial research or the importance of Cooperative Group research in advancing the field of oncology research and patient care. In addition, physician scientists are less likely than basic scientists to have protected paid time to perform their research (NCI, 2005a). In particular, clinical research—such as involvement in the Cooperative Group Program—requires a team orientation. According to the President’s Cancer Panel, team approaches are the paradigm for achieving progress in translating basic science discoveries into applications that improve clinical practice (NCI, 2005a). However, traditional academic metrics and incen- tives structures tend to reward individuals rather than teams (Altshuler and Altshuler, 2004). For example, current scientific journal authorship guide- lines allow for singling out only first and last authors as leaders in publica- tion. Altshuler and Altshuler called for a deconstruction of the author list so that the particular contributions of each author may be indicated. It is also possible to list all investigators instead of just the principal investigator in the Computer Retrieval of Information on Scientific Projects database3 (IOM, 2009b). Because traditional academic metrics focus on individual accomplish- ments, investigators may participate minimally in team-oriented research activities. For example, investigators may limit participation in multi- institutional, late-phase clinical trials, such as those conducted through the Cooperative Group Program, so that they can dedicate more time to activities that are viewed as having higher value within their institution in terms of both funding and recognition. Academic clinicians are incentiv- ized to conduct smaller, individual investigator-initiated studies that lead to R01 grants, the primary mechanism of support for NIH-funded cancer research (NCI, 2005a). The inadequate value given to team-based, clinical research in academic tenure and promotion decisions prevents more robust participation in Cooperative Group trials. Therefore, the committee rec- ommends that academic medical centers develop policies and evaluation 3 The Computer Retrieval of Information on Scientific Projects is a biomedical database that contains information on U.S. Department of Health and Human Services-supported research projects and programs.

OCR for page 191
200 A NATIONAL CANCER CLINICAL TRIALS SySTEM metrics that recognize and reward clinical/team research in promotion and tenure decisions. Similar to the committee’s recommendation, the Opera- tional Efficiency Working Group of the Clinical Trials Advisory Committee recommended that NCI create incentives for institutions to include accrual in Cooperative Group clinical trials as a service criterion for tenure and promotion. Although there are mechanisms to support team-oriented research (such as NIH P01 Program Project, P30 Center, P50 SPORE grants, and U54 Cooperative Agreements4), they are a small fraction of the funding for individual project grants (NCI, 2005a). Without incentives to support team- oriented clinical research, the translation of discoveries in basic science into clinical knowledge and care will be slowed (Schrier, 1997). Recognizing the impact of this dilemma on the Cooperative Group Program, the CTWG recommended that NCI and academic incentives be realigned so that they promote collaborative team science (NCI, 2005b). The Cooperative Group Program relies on clinical, team-oriented research. However, the committee found that cancer center Support Grants (CCSGs), which support the research capacities of cancer centers, do not adequately incentivize participation in multi-institutional Cooperative Group trials. Rather, CCSG review criteria favor investigator-initiated tri- als emerging from basic discoveries within a cancer center’s own institu- tion. To fulfill current CCSG review guidelines, cancer centers that have a clinical component are expected to provide leadership for and participate in Cooperative Group trials.5 Part of the CCSG review is the assessment of a cancer center’s funding base. The U10 award that supports a Cooperative Group’s operations and statistical offices is considered equivalently with other peer-reviewed funding. However, the per case reimbursements that the Cooperative Groups provide to cancer centers are not counted in the CCSG review’s benchmark ratio,6 part of the funding base assessment that helps to determine the CCSG award amount. Because per case reimbursements are not adequately rewarded in CCSG reviews and do not fully cover the costs 4 The P01 Research Program Project supports integrated, multi-project research projects involving a number of independent investigators who share knowledge and common resources. The P30 Center Core Grants supports shared resources and facilities for categorical research using a multidisciplinary approach, or for investigators from the same discipline who focus on a common research problem. The P50 Specialized Center supports basic and clinical research and development, with a multidisciplinary focus on a specific disease entity or biomedical problem area. Like the P50 award, the U54 cooperative agreement supports basic and clini- cal research and development, with a multidisciplinary focus on a specific disease entity or biomedical problem area (HHS, 2010). 5 Personal communication, Linda Weiss, National Cancer Institute, November 2, 2009. 6 The Cancer Centers Program is currently reviewing the CCSG guidelines and may not include a benchmark ratio in the next version, but it is not clear what it will be replaced with. Personal communication, Linda Weiss, National Cancer Institute, November 5, 2009.

OCR for page 191
201 PHySICIAN AND PATIENT PARTICIPATION of participation in a clinical trial, cancer center directors may discourage their investigators from actively participating in Cooperative Group tri- als. To improve participation in Cooperative Group trials, the committee recommends that NCI recognize and reward Cooperative Group efforts in Cancer Center Support Grant (CCSG; P30) site visits, and allow the CCSG research base to include the federal per case funding received by cancer centers that participate in Cooperative Group trials. Ensuring the Clinical Investigator Pipeline The pipeline of physician scientists is decreasing. In the United States, the physician scientist population is smaller now than it was 25 years ago (Ley and Rosenberg, 2005). In 1983, there were 18,535 physician scientists in the United States; by 1998, that number had fallen to 14,479, a 22 per- cent decline (Varki and Rosenberg, 2003). Reasons for the shrinking pipe- line include the changing health care environment, the complexity of rapid advances in biomedical science and the consequent retooling necessary after clinical training, the length and rigor of research training required, the scarcity of funding for subspecialty training positions, competition for research funding, the perception that successful clinician scientists are those who focus on basic research and not clinical research, and senior faculty pessimism over the survival of physician scientists (Schrier, 1997). Some progress toward reversing the trend has occurred. In 1998, NIH established career development rewards (the K23 and K24 grant programs) for young and established physicians undertaking clinical research. In 2002, NIH offered competitive loan repayment programs that offered at least 2 years of tax-free debt relief for young scientists with commitments to clini- cally oriented research training (Ley and Rosenberg, 2005). Several awards specifically focus on strengthening the physician scientist pipeline for oncol- ogy. For example, through the Damon Runyon Clinical Investigator Award, early career physician scientists receive $450,000 to support the develop- ment of their cancer research program to conduct patient-oriented cancer research under the mentorship of leading scientists (Damon Runyon Cancer Research Foundation, 2009). In addition, The ASCO Cancer Foundation (TACF) and NCI partnered to provide funding and recognition of clinical investigators leading cancer research programs at academic cancer centers through the NCI-TACF clinical investigator award. The award provides 2 years of salary support (10 to 15 percent) for up to 10 clinical investiga- tors who play leadership roles in clinical trials at NCI-designated cancer centers. The intention of the award is to recognize clinical investigators who are not principal investigators on an NIH grant but who are actively involved in NCI-funded collaborative clinical trials, promoting collab- orative team science and the retention of clinical investigators (NCI-TACF

OCR for page 191
22 A NATIONAL CANCER CLINICAL TRIALS SySTEM munity practices and academia. An important first step is ensuring that physicians receive reimbursement commensurate with the level of time and resources involved in conducting clinical trial research. The many duties required of physicians and other key research staff, such as research nurses and clinical research associates, to participate in clinical trials are costly in terms of both time and resources. Even in cases where 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. Before a trial can be opened at a particular site, much work must be done to ensure compliance with federal regulations governing human sub- jects research. Once a trial is opened, a significant amount of time is spent discussing potential trial options with patients. If a patient enrolls, the data collection and documentation requirements are substantially more onerous than for patients receiving standard therapy outside of a trial. Therefore, NCI should increase the per case reimbursement rate. A substantial increase in the NCI per case reimbursement would constitute a major step toward aligning the incentives of physicians with those of their patients who wish to participate in clinical trials. The per case reimburse- ment has been set at $2,000 since 1999, even though the median costs are estimated at $3,500 to $6,000 per patient. 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. NCI should also provide funding to site and trial principal investigators to cover the time they need to develop and oversee approved clinical trials. The provi- sion of funds for principal investigators to cover the time needed to develop and oversee approved trials could improve the speed and quality of trials and encourage greater participation. In addition, the American Medical Association should establish new CPT codes, reimbursed by CMS, private insurers, and other third-party payors, to pay an enhanced reimbursement for offering, enrolling, managing, and following a patient in a clinical trial. New CPT codes, with a higher reimbursement rate that acknowledges the additional time and resources needed to counsel and care for a patient in a clinical trial, would address an important deterrent to physician participa- tion in clinical trials. With a proper definition of eligible trials, use of such a code could be easily audited. Ensuring that physicians are recognized, rewarded, and appropriately trained in clinical trial research is also essential to encouraging participa- tion. All stakeholders, including academic medical centers, community practices, professional societies, and NCI, should work to ensure that clinical investigators have adequate training and mentoring, paid protected research time, the necessary resources, and recognition. 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

OCR for page 191
22 PHySICIAN AND PATIENT PARTICIPATION 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. Clinical trials help to raise the standard of care in the community by setting examples, and they have educational and training value for the oncologists involved, as physicians gain early knowledge of new drugs and gain experience with delivering complex therapies. One way to recognize investigators is through a certification program. NCI should work with a nonprofit foundation to develop a certification program and registry, as recommended by the CTWG. A certification program for all research staff (including physicians, nurses, clinical research associates, pharmacists, etc.) would recognize the valuable contributions these professionals make to improving patient care. In addition, academic medical centers should develop policies and evaluation metrics that recognize and reward clinical and team research in promotion and tenure decisions. The large-scale, multi-institutional trials that are the hallmark of the Cooperative Group Program require a team approach to research. However, career advancement in the field has tra- ditionally focused on individual accomplishment. Collaborative work is not adequately recognized, rewarded, or supported in the current system. Furthermore, clinical investigation is often accorded less value than either basic research or patient care. This must change if we wish to have talented individuals embark on a career that entails active participation in clinical investigation, in cancer as well as other diseases. NCI should recognize and reward Cooperative Group efforts in Cancer Center Support Grant (CCSG; P30) site visits, and allow the CCSG research base to include the federal per case funding required by cancer centers that participate in support of Cooperative Group trials. CCSG review criteria do not adequately incen- tivize participation in multi-institutional Cooperative Group trials, and instead favor individual investigator-initiated trials emerging from basic dis- coveries within a cancer center’s own institution. Recognizing the per case reimbursements for Cooperative Group Trials in the CCSG assessment of a cancer center’s funding base would acknowledge the importance of patient accrual in these trials and encourage broader participation at those centers. Clinical research is a complex endeavor that requires training, mentoring, and paid time set aside for research to master and apply the skills needed to undertake innovative trials. If cancer care is to be evidence-based and relevant to the diverse patient population, it is important for coverage policies to encourage rather than deter patient enrollment in trials. Therefore, the committee recommends that health care payment policies value the care provided to patients in clinical trials and adequately compensate that care. Inadequate health care coverage is a major deterrent to participation in trials, for patients as well as physicians. Health care insurers traditionally have not paid for “experi-

OCR for page 191
22 A NATIONAL CANCER CLINICAL TRIALS SySTEM mental therapy.” However, much of the care provided to cancer patients is similar regardless of whether the patient is receiving a standard or experi- mental drug. Some insurers and states acknowledge this and reimburse the routine clinical care of patients enrolled in trials, while others do not. Poli- cies at CMS regarding coverage of care in clinical trials have been in flux recently, and, absent National Coverage Decisions, may not be nationally uniform because fiscal intermediaries and carriers have some discretion on coverage, which can cause regional variation and inconsistency. Further- more, the provisions of the ERISA, which places the regulation of employee benefit plans (including health plans) primarily under federal jurisdiction for about 131 million people, preempts state laws governing such things as access to care and mandated coverage. Thus, coverage of care in clinical trials is variable and may be uncer- tain. Patients who are interested and willing to enroll in a trial may decline due to an inability to pay for care that is not, or may not be, covered. Oth- ers might still enroll, but then may experience significant financial hardship as a result. If such patients drop out of the trial, the scientific integrity of the trial can be compromised due to inferential problems that result from missing data. In order to facilitate patient and physician participation in clinical trials, more consistent policies regarding patient care costs are needed. The committee recommends that CMS (via a national coverage decision), federal and state health benefits plans, and private health insurers establish consistent payment policies to cover all patient care costs (except for study-related costs, such as study drugs, devices, and tests, which should be paid for by the manufacturer) in clinical trials approved through the NCI prioritization mechanism, without having to pay for experimental therapies administered to patients outside of a clinical trial. Currently, many patients who are not enrolled in trials receive experimental therapy and expect coverage for it. Any such limitation in coverage should not affect off-label use that is backed by evidence from clinical trials published in the scientific literature, as evidence-based off-label use constitutes standard of care for many cancer therapies and is therefore not experimental. In addition, the u.S. Congress should amend ERISA to prohibit health plans from denying (or from limiting or imposing additional conditions on) coverage for routine care associated with clinical trial participation. The committee’s recommended approach is analogous to the “coverage with evi- dence development” mechanism that has occasionally been used by CMS, in which coverage is only provided within the context of a trial. However, taking steps to align the incentives of patients and providers to participate in clinical trials may not be effective unless more is done to educate patients about the availability and value of clinical trials. The com- mittee recommends that CMS, federal and state health benefit plans, and private health insurers work with health care providers to educate patients

OCR for page 191
22 PHySICIAN AND PATIENT PARTICIPATION more effectively about the availability, payment coverage, and value of clinical trials. Educational efforts should focus on making the general popu- lation more aware of clinical trials. One reason is that it can be difficult for patients to sort through a large volume of new information and make complex decisions having just received a diagnosis of a life-threatening illness. Patients often lack comprehensive and reliable information about clinical trials and may not be able to identify trials they might be eligible for. Patients value reliable information from trusted sources, including family members, so appropriate education efforts could provide useful information that would allow patients to make informed choices about trial participa- tion. In addition, as noted in more detail below, user-friendly electronic tools would increase awareness of trials and make it easier for physicians and patients to enroll in the most appropriate studies. To ensure the rapid conduct and completion of clinical trials, the enrollment of patients onto clinical trials must be improved. At the same time, it is essential that clinical trials conducted by the Cooperative Groups maintain high quality standards. Thus, NCI, Cooperative Groups, and physicians should take steps to increase the speed, volume, and diversity of patient accrual and to ensure high-quality performance at all sites par- ticipating in Cooperative Group trials. In addition, they should encourage greater enrollment in high-priority trials, regardless of where the trial originated. Currently, the majority of patients who participate in clinical trials are enrolled by a small percentage of participating sites. Many sites enroll only a few patients in Cooperative Group clinical trials—enough to maintain their status as investigators. These circumstances can contribute to the underrepresentation in clinical trials of minority and underserved popu- lations. Given the importance of trials in generating the evidence needed for making the best treatment decisions, more physicians should be encour- aged to include trial participation in their clinical practice. As mentioned previously, providing adequate case reimbursement would help to align physician and patient incentives and facilitate higher accrual at participat- ing sites. However, another obstacle to increasing patient enrollment is that physicians may lack timely and easy-to-access information about clinical trials that would be appropriate for their patients. Some public databases with information about clinical trials exist, but in current form, may not adequately serve the information needs of physicians and patients as they are not in the normal workflow of a busy clinical practice. Therefore, the committee recommends that NCI, Cooperative Groups, and physicians develop electronic tools that cue physicians practicing oncology via EMR systems about trials for which a particular patient is eligible. User-friendly electronic tools, available with the right features for physician workflow, would increase awareness of trials and make it easier for physicians and patients to enroll in the most appropriate studies. Complementing increased

OCR for page 191
22 A NATIONAL CANCER CLINICAL TRIALS SySTEM awareness, the committee encourages physicians to incorporate clinical trial involvement into their practices. Physicians should strive to make participa- tion in clinical trials a key component of clinical practice and to achieve the ASCO exemplary attributes for academic and community clinical trial sites, including high accrual rates of 10 percent or more. Eligibility criteria present another challenge to increasing enrollment. Historically, stringent eligibility criteria have excluded many patients, including, for example, those with prior cancers or certain prior treat- ments. However, it has been argued that adoption of less-restrictive eligi- bility criteria for most studies would permit more rapid accrual and also allow broader generalizations, better mimic medical practice, and reduce complexity and costs, without compromising patient safety or requiring major increases in sample size. To facilitate accrual speed, volume, and diversity, NCI, Cooperative Groups, and physicians should encourage the development of patient eligibility criteria that allow the broadest partici- pation possible. Greater involvement by patient advocates could help to facilitate this change. Thus, the committee encourages greater participation of patient advocates in trial concept development and accrual planning, and partnerships with patient advocacy organizations to support accrual efforts. Advocates also provide valuable input to study design and procedures, safety and confidentiality issues, feasibility, informed consent processes, and other factors important to potential research participants to help facilitate the development, implementation, and recruitment processes. Ensuring consistent quality at participating trial sites is also important. Site credentialing requirements vary among the Cooperative Groups, mak- ing it difficult for sites that wish to engage with multiple groups. Therefore, the committee recommends that NCI, Cooperative Groups, and physicians establish a centralized credentialing system for participating sites and elimi- nate investigators and sites with low rates of accrual or inadequate data management skills or quality. A centralized credentialing system, perhaps outsourced to an independent entity, would increase consistency and qual- ity across sites, and eliminate the burden of re-credentialing. Such a system would also facilitate greater enrollment in high-priority trials, regardless of where the trial originated, because sites would be credentialed to participate in any Cooperative Group Trial. Moreover, elimination of low accruing sites would reduce costs and improve the efficiency of the trials system. REFERENCES 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. Agres, T. 2005. Clinical trials trickling away. Drug Discovery and Development, July 5.

OCR for page 191
22 PHySICIAN AND PATIENT PARTICIPATION AHRQ (Agency for Healthcare Research and Quality). 2009. Horizon Scan: To What Extent Do Changes in Third-Party Payment Affect Clinical Trials and the Evidence Base? Rock- ville, MD: Agency for Healthcare Research and Quality. Albrecht, T. L., S. S. Eggly, M. E. J. Gleason, F. W. K. Harper, T. S. Foster, A. M. Peterson, H. Orom, L. A. Penner, and J. C. Ruckdeschel. 2008. The influence of clinical commu- nication on patients’ decision making about clinical trials. Journal of Clinical Oncology 26(16):2666–2673. Altshuler, J. S., and D. Altshuler. 2004. Organizational challenges in clinical genomic research. Nature 429(6990):478–481. Andrews, N., J. E. Burris, T. R. Cech, B. S. Coller, W. F. Crowley, E. K. Gallin, K. L. Kelner, D. G. Kirch, A. I. Leshner, C. D. Morris, F. T. Nguyen, J. Oates, and N. S. Sung. 2009. Translational careers. Science 324(5929):855. Arnold, K., and B. Vastag. 2000. Medicare to cover routine care costs in clinical trials. Journal of the National Cancer Institute 92(13):1032. ASCO (American Society of Clinical Oncology). 2008. Community Oncology Research Grant. http://www.ascocancerfoundation.org/TACF/Grants/Grant+Opportunities/Community+ Oncology+Research+Grant (accessed September 24, 2009). ASCO certification program emphasizes quality of care. 2009. The Cancer Letter 35(22):6. Bennett, C. L., T. J. Stinson, V. Vogel, L. Robertson, D. Leedy, P. O’Brien, J. Hobbs, T. Sutton, J. C. Ruckdeschel, T. N. Chirikos, R. S. Weiner, M. M. Ramsey, and M. S. Wicha. 2000. Evaluating the financial impact of clinical trials in oncology: Results from a pilot study from the Association of American Cancer Institutes/Northwestern University Clinical Trials Costs and Charges Project. Journal of Clinical Oncology 18(15):2805–2810. Bennett, C. L., J. R. Adams, K. S. Knox, A. M. Kelahan, S. M. Silver, and J. S. Bailes. 2001. Clinical trials: Are they a good buy? Journal of Clinical Oncology 19(23):4330–4339. Blayney, D. W. 2009. Results of Cooperative Group Site Poll. Presented at the NCI National Cancer Advisory Board Meeting, September, Bethesda, MD. Braunholtz, D. A., S. J. L. Edwards, and R. J. Lilford. 2001. Are randomized clinical trials good for us (in the short term)? Evidence for a “trial effect.” Journal of Clinical Epide- miology 54(3):217–224. Butler, P. A. 2000. ERISA and state health care access initiatives: Opportunities and obstacles. New York: The Commonwealth Fund. CALGB (Cancer and Leukemia Group B). 2009. Cancer and Leukemia Group B: Tomor- row’s cancer treatments today. CALGB Membership Information. http://www.calgb.org/ Public/membership/membership.php (accessed September 29, 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 and Philadelphia, PA: Coalition of Cancer Cooperative Groups. Chaikind, H. R. 2003. ERISA Regulation of Health Plans: Fact Sheet. Washington, DC: Congressional Research Service. CMS (Centers for Medicare & Medicaid Services). 2009. NCD for Routine Costs in Clinical Trials (10.1). http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=310.1&ncd_version=2 &basket=ncd%3A310.1%3A2%3ARoutine+Costs+in+Clinical+Trials (accessed October 25, 2009). Coalition of Cancer Cooperative Groups. 2006. Baseline Study of Patient Accrual onto Publicly Sponsored Trials: An Analysis Conducted for the Global Access Project of the National Patient Advocate Foundation. Philadelphia, PA: Coalition of Cancer Coopera- tive Groups (http://www.CancerTrialsHelp.org).

OCR for page 191
20 A NATIONAL CANCER CLINICAL TRIALS SySTEM Colavecchio, S. 2010. Insurers Agree to Cover Patients in Clinical Trials. Insurance Companies Will Have to Continue Routine Coverage for Cancer Patients Who Participate in Clinical Trials, Under a New State Agreement. The Miami Herald, January 14. http://www.miami herald.com/516/story/1424009.html (accessed February 1, 2010). Collyar, D. 2008. An essential partnership: Patient advocates and cooperative groups. Semi- nars in Oncology 35(5):553–555. Colon-Otero, G., R. C. Smallridge, L. J. Solberg, T. D. Keith, T. A. Woodward, F. B. Willis, and A. N. Dunn. 2007. Disparities in participation in cancer clinical trials in the United States: A symptom of a healthcare system in crisis. Cancer 112(3):447–454. Comis, R. 2003. A brief history of the research and treatment of lung cancer from 1970–2003. International Journal of Clinical Oncology 8(4):230–233. Comis, R. 2007. The Coalition of Cancer Cooperative Groups. Journal of Oncology Practice 3(5):280. Comis, R. L., J. D. Miller, C. R. Aldige, L. Kregs, and E. Stoval. 2003. Public attitudes toward participation in cancer clinical trials. Journal of Clinical Oncology 21(5):830–835. Comis, R. L., J. D. Miller, D. D. Colaizzi, and L. G. Kimmel. 2009. Physician-related factors involved in patient decisions to enroll onto cancer clinical trials. Journal of Oncology Practice 5(2):50–56. Co-payments to rise as access to drugs tightens for patients on Medicare Part D. 2008. The Cancer Letter 23(11):1, 4. Cox, K., and J. McGarry. 2003. Why patients don’t take part in cancer clinical trials: An overview of the literature. European Journal of Cancer Care 12:114–122. CTEP (Cancer Therapy Evaluation Program). 2006. National Cancer Institute Clinical Trials Cooperative Group Program Guidelines. Bethesda, MD: National Cancer Institute. Damon Runyon Cancer Research Foundation. 2009. Clinical Investigator Award Overview. http://www.damonrunyon.org/for_scientists/more/clinical_investigator_award_overview (accessed December 17, 2009). Davis, S., S. F. Schulman, L. D. Hill, R. D. Pinkham, L. P. Johnson, T. W. Jones, H. B. J. Kellogg, H. M. Radke, W. W. Sikkema, P. C. Jolly, and S. P. Hammar. 1985. Participants in pro- spective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials. Cancer 56(7):1710–1718. De Angelis, C., J. M. Drazen, F. A. Frizelle, C. Huag, J. Hoey, R. Horton, S. Kotzin, C. Laine, A. Marusic, A. J. P. M. Overbeke, T. V. Schroeder, H. C. Sox, and M. B. Van der Weyden. 2004. Trial registration: A statement from the International Committee of Medical Jour- nal Editors. New England Journal of Medicine 351(12):1250–1251. Demmy, T. L., J. M. Yasko, D. E. Collyar, and M. L. Katz. 2004. Managing accrual in coopera- tive group clinical trials. Journal of Clinical Oncology 22(15):2997–3002. Doroshow, J. H., and G. Hortobagyi. 2010. Operation Efficiency Working Group: Compress- ing the Timeline for Cancer Clinical Trial Activation. Final report. Presented at the Clinical Trials and Translational Research Advisory Committee Meeting, March 2010, Bethesda, MD. EDICT. 2008. The EDICT Project: Policy Recommendations to Eliminate Disparities in Clini- cal Trials. Houston, TX: EDICT Project. Ellis, P. M. 2000. Attitudes towards and participation in randomised clinical trials in oncology: A review of the literature. Annals of Oncology 11:939–945. EmergingMed. 2009. EmergingMed: About Us. http://www.emergingmed.com/pub_aboutus. asp (accessed October 27, 2009). ENACCT-CCPH (Education Network to Advance Cancer Clinical Trials-Community-Campus Partnerships for Health). 2008. Communities as Partners in Cancer Clinical Trials: Changing Research, Practice, and Policy. Bethesda, MD: Education Network to Advance Cancer Clinical Trials; Seattle, WA: Community Campus Partnerships for Health.

OCR for page 191
21 PHySICIAN AND PATIENT PARTICIPATION Fitterman, L. K. 2008. Clinical Trial Policy. Presented at the NCPF Workshop on Multi-Center Phase III Clinical Trials and NCI Cooperative Groups, Washington, DC. Florida Clinical Trial Compact. 2010. Agreement to Reduce Cancer Morbidity and Mortality in Florida. http://www.efrwc.org/_Temp/Clinical%20Trial%20Agreement%20Final.pdf (accessed February 1, 2010). GAO (Government Accounting Office). 1999. NIH Clinical Trials: Various Factors Affect Patient Participation. Washington, DC: Government Accounting Office. George, S. L. 1996. Reducing patient eligibility criteria in cancer clinical trials. Journal of Clinical Oncology 14(4):1364–1370. Getz, K. A. 2007. Global clinical trials activity in the details. Applied Clinical Trials, September 1, pp. 42–44. http://appliedclinicaltrialsonline.findpharma.com/applied- clinicaltrials/Regulatory/Global-Clinical-Trials-Activity-in-the-Details/ArticleStandard/ Article/detail/453243 (accessed April 8, 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. Goldman, D. P., M. L. Schoenbaum, A. L. Potosky, J. C. Weeks, S. H. Berry, J. J. Escarce, B. A. Weidmer, M. L. Kilgore, N. Wagle, J. L. Adams, R. A. Figlin, J. H. Lewis, J. Cohen, R. Kaplan, and M. S. McCabe. 2001. Measuring the incremental cost of clinical cancer research. Journal of Clinical Oncology 19(1):105–110. Goldman, D. P., S. H. Berry, M. S. McCabe, M. L. Kilgore, A. L. Potosky, M. L. Schoenbaum, M. Schonlau, J. C. Weeks, R. Kaplan, and J. J. Escarce. 2003. Incremental treatment costs in National Cancer Institute-sponsored clinical trials. Journal of the American Medical Association 289(22):2970–2977. HarrisInteractive. 2001. Misconceptions and lack of awareness greatly reduce recruitment for cancer clinical trials. Health Care News 1(3):1–3. HHS (U.S. Department of Health and Human Services). 2009. Health Information Technology for the Future of Health and Care: Meaningful Use. http://healthit.hhs.gov/portal/server. pt?open=512&objID=1325&parentname=CommunityPage&parentid=1&mode=2 (ac- cessed October 27, 2009). HHS. 2010. Types of Grant Programs. http://grants.nih.gov/grants/funding/funding_program. htm (accessed February 1, 2010). IOM (Institute of Medicine). 1999. The Unequal Burden of Cancer: An Assessment of NIH Research Programs for Ethnic Minorities and the Medically Underserved. Washington, DC: National Academy Press. IOM. 2000. Extending Medicare Reimbursement in Clinical Trials. Washington, DC: National Academy Press. IOM. 2006. Developing a National Registry of Pharmacologic and Biologic Clinical Trials: Workshop Report. Washington, 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. Multi-Center Phase III Clinical Trials and NCI Cooperative Groups: Workshop Summary. Washington, DC: The National Academies Press. Jha, A. K., T. G. Ferris, K. Donelan, C. DesRoches, A. Shields, S. Rosenbaum, and D. Blumenthal. 2006. How common are electronic health records in the United States? A summary of the evidence. Health Affairs 25(6):w496–w507. KFF (Kaiser Family Foundation). 2009. Medicare Fact Sheet: Medicare Advantage. Menlo Park, CA: Kaiser Family Foundation. Kolata, G., and K. Eichenwald. 1999. Group of insurers will pay for experimental cancer therapy. The New york Times, December 16, p. C1.

OCR for page 191
22 A NATIONAL CANCER CLINICAL TRIALS SySTEM Ley, T. J., and L. E. Rosenberg. 2005. The physician-scientist career pipeline in 2005: Build it, and they will come. Journal of the American Medical Association 294(11):1343–1351. Lin, C. J., D. E. Heron, and K. Connelly. 2008. Does Medicare HMO reimbursement policy hinder clinical trial participation. International Journal of Radiation Oncology*Biology*Physics 72(1 Suppl. 1):S138. Malakoff, D. 2008. Spiraling costs threaten gridlock. Science 322(5899):210–213. Mansour, E. G. 1994. Barriers to clinical trials. Part III. Knowledge and attitudes of health care providers. Cancer 74(Suppl. 9):2672–2675. Masys, D. 2009. Electronic Data Capture and Analysis by NCI Cooperative Groups. Presented at the NCPF workshop on Cancer Clinical Trials and the NCI Cooperative Group Pro- gram, Washington, DC. Mathieu, S., I. Boutron, D. Moher, D. G. Altman, and P. Ravaud. 2009. Comparison of registered and published primary outcomes in randomized control trials. Journal of the American Medical Association 302(9):977–984. 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. Mechanic, R. E., and A. Dobson. 1996. The impact of managed care on clinical research: A preliminary investigation. Health Affairs 15(3):72–89. Melisko, M. E., F. Hassin, L. Metzroth, D. H. Moore, B. Brown, K. Patel, H. S. Rugo, and D. Tripathy. 2005. Patient and physician attitudes toward breast cancer clinical trials: Devel- oping interventions based on understanding barriers. Clinical Breast Cancer 6(1):45–54. Mooney, M. 2008. Cooperative Group Clinical Trials Complexity Funding: Model Devel- opment and Trial Selection Process. Presented at the Clinical Trials and Translational Research Advisory Committee Meeting, December 8, 2008, Bethesda, MD. Murphy, L., S. Sadownik, C. Ford, V. Barton, C. Schmidt, and S. Barber. 2008. Cost Shar- ing for Cancer Patients in Medicare, 200. Washington, DC: Avalere Health, American Cancer Society Cancer Action Network. NCCN (National Comprehensive Cancer Network). 2009. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. http://www.nccn.org/professionals/ physician_gls/f_guidelines.asp (accessed December 4, 2009). 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. 2001. Cancer Clinical Trials: The Basic Workbook. Bethesda, MD: National Cancer Institute. 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. 2009a. Clinical Trials Covered Under the Medicare Anti-Cancer Drugs National Cov- erage Decision. http://www.cancer.gov/clinicaltrials/developments/NCD179N (accessed October 25, 2009). NCI. 2009b. Help Using the NCI Clinical Trials Search Form. http://www.nci.nih.gov/clini- caltrials/search-form-help/page1 (accessed October 27, 2009). NCI-TACF clinical investigator award. 2009. The Cancer Letter 35(26):8. NCSL (National Conference of State Legislatures). 2009. Clinical Trials: What Are States Doing? August 200 Update. http://www.ncsl.org/default.aspx?tabid=14331 (accessed October 22, 2009). NIH (National Institutes of Health). 2008. About ClinicalTrials.gov. http://clinicaltrials.gov/ ct2/info/about (accessed October 27, 2009).

OCR for page 191
2 PHySICIAN AND PATIENT PARTICIPATION Normile, D. 2008. The promise and pitfalls of clinical trials overseas. Science 322(5899): 214–216. Peppercorn, J., J. C. Weeks, E. F. Cook, and S. Joffe. 2004. Comparison of outcomes in cancer patients treated within and outside clinical trials: Conceptual framework and structured review. The Lancet 363(9405):263–270. Reaman, G. 2009. Children’s Oncology Group: A National/International Infrastructure for Pediatric Cancer Clinical Translational Research. Presented to the Institute of Medicine Committee on Cancer Clinical Trials and the NCI Cooperative Group Program, April 23, 2009, Washington, DC. Robinson, W. R., J. Ritter, A. S. Rogers, S. Tedjarati, and C. Lieberenz. 2009. Clinical trial participation is associated with improved outcome in women with ovarian cancer. Inter- national Journal of Gynecological Cancer 19(1):124–128. Roy, P., G. V. Hudson, B. V. Hudson, J. Esteve, and A. J. Swerdlow. 2000. Long-term survival in Hodgkin’s disease patients: A comparison of relative survival in patients in trials and those recorded in population-based cancer registries. European Journal of Cancer 36(3):384–389. Sateren, W. B., E. L. Trimble, J. Abrams, O. W. Brawley, N. Breen, L. Ford, M. S. McCabe, R. Kaplan, M. Smith, R. Ungerleider, and M. Christian. 2002. How sociodemographics, presence of oncology specialists, and hospital cancer programs affect accrual to cancer treatment trials. Journal of Clinical Oncology 20(8):2109–2017. Schain, W. S. 1994. Barriers to clinical trials. Part II. Knowledge and attitudes of potential participants. Cancer 74(Suppl. 9):2666–2671. Schrier, R. W. 1997. Ensuring the survival of the clinician-scientist. Academic Medicine 72(7):589–594. Siminoff, L. A., A. Zhang, N. Colabianchi, C. M. S. Sturm, and Q. Shen. 2000. Factors that predict the referral of breast cancer patients onto clinical trials by their surgeons and medical oncologists. Journal of Clinical Oncology 18(6):1203–1211. Somkin, C. P., A. Altschuler, L. Ackerson, A. M. Geiger, S. M. Greene, J. Mouchawar, J. Holup, L. Fehrenbacher, A. Nelson, A. Glass, J. Polikoff, S. Tishler, C. Schmidt, T. Field, and E. Wagner. 2005. Organizational barriers to physician participation in cancer clinical trials. The American Journal of Managed Care 11(7):413–421. Stiller, C. A. 1994. Centralised treatment, entry to trials and survival. British Journal of Cancer 70(2):352–362. Taylor, H. 2004. Most physicians do not participate in clinical trials because of lack of op- portunity, time, personnel support and resources. Harris Interactive: Health Care News 4(9):1–8. Underwood, S. M. 2000. Minorities, women, and clinical cancer research: The charge, promise, and challenge. Association of Educational Psychologists Journal 10(Suppl. 8):s4–s12. Varki, A., and L. E. Rosenberg. 2003. Emerging opportunities and career paths for the young physician-scientist. Nature Medicine 8(5):437–439. Verheggen, F. W. S. M., F. Nieman, and R. Jonkers. 1998. Determinants of patient participa- participa- tion in clinical studies requiring informed consent: Why patients enter a clinical trial. Patient Education and Counselling 35:111–125. Vist, G. E., K. B. Hagen, P. J. Devereaux, D. Bryant, D. T. Kristoffersen, and A. D. Oxman. 2005. Systematic review to determine whether participation in a trial influences outcome. British Medical Journal 330(7501):1175–1181. Vist, G. E. D. Bryant, L. Somerville, T. Birminghem, A. D. Oxman. 2008. Outcomes of patients who participate in randomized controlled trials compared to similar patients receiving similar interventions who do not participate. Cochrane Database of Systematic Reviews Jul 16 (3):MR000009.

OCR for page 191
2 A NATIONAL CANCER CLINICAL TRIALS SySTEM Wallace, P. 2009. Kaiser Permanente Oncology-Specific Care Management Systems. Presented at the NCPF Workshop on A Foundation for Evidence-Driven Practice: A Rapid Learning System for Cancer Care, Washington, DC. Zarin, D. A., and T. Tse. 2008. Moving toward transparency of clinical trials. Science 319 (5868):1340–1342. Zarin, D. A., T. Tse, and N. C. Ide. 2005. Trial registration at ClinicalTrials.gov between May and October 2005. New England Journal of Medicine 353(26):2779–2787. Zon, R., N. J. Meropol, R. B. Catalano, and R. L. Schilsky. 2008. American Society of Clini- Clini- cal Oncology statement on minimum standards and exemplary attributes of clinical trial sites. Journal of Clinical Oncology 26(15):2562–2567.