6
The Necessary Environment for Research and Development

While the public impatiently awaits new technologies and headlines, medical researchers bemoan the “national crisis.” The crisis is not in discovery and invention, but rather in getting those discoveries to the public.

RN Rosenberg, JAMA 2003

Basic research lays the foundation for the discovery and invention of new medical technologies, but the path from discovery to adoption is long and often full of unexpected turns. The value of any new technology must be demonstrated through a series of increasingly stringent steps, each of which can take years.aFigure 6-1 illustrates the pathway of medical technology development from discovery to adoption in clinical practice.

Once a technology reaches the prototype, or investigational, stage, it is typically tested in small clinical studies, usually involving fewer than 50 subjects. In most cases, a technology must pass Food and Drug Administration (FDA) review for safety and effectiveness before it can be marketed. Because most technologies are affordable only if they are covered by health care insurance, most will not be adopted in clinical practice unless their use is deemed “reasonable and necessary,” by either the Centers for Medicare & Medicaid Services (CMS) or private insurance companies. Practically speaking, that means that the technology must be shown to improve outcomes. The time from discovery and invention to clinical use is a source of great concern and frustration to technology developers, as well as members of the public who eagerly await these advances, none more impatiently than those whose mission is to reduce the toll of breast cancer.

a  

“Technology” is used here in the broadest sense and includes biology, drugs, software, devices, and procedures.



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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis 6 The Necessary Environment for Research and Development While the public impatiently awaits new technologies and headlines, medical researchers bemoan the “national crisis.” The crisis is not in discovery and invention, but rather in getting those discoveries to the public. RN Rosenberg, JAMA 2003 Basic research lays the foundation for the discovery and invention of new medical technologies, but the path from discovery to adoption is long and often full of unexpected turns. The value of any new technology must be demonstrated through a series of increasingly stringent steps, each of which can take years.a Figure 6-1 illustrates the pathway of medical technology development from discovery to adoption in clinical practice. Once a technology reaches the prototype, or investigational, stage, it is typically tested in small clinical studies, usually involving fewer than 50 subjects. In most cases, a technology must pass Food and Drug Administration (FDA) review for safety and effectiveness before it can be marketed. Because most technologies are affordable only if they are covered by health care insurance, most will not be adopted in clinical practice unless their use is deemed “reasonable and necessary,” by either the Centers for Medicare & Medicaid Services (CMS) or private insurance companies. Practically speaking, that means that the technology must be shown to improve outcomes. The time from discovery and invention to clinical use is a source of great concern and frustration to technology developers, as well as members of the public who eagerly await these advances, none more impatiently than those whose mission is to reduce the toll of breast cancer. a   “Technology” is used here in the broadest sense and includes biology, drugs, software, devices, and procedures.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis FIGURE 6-1 Pathway of medical technology development. This chapter describes the stages of technology development and considers the degree to which there are obstacles that cause unreasonable delays and proposals for reducing those obstacles. Avoidable pitfalls, such as clinical studies designed so poorly that they fail to provide clear answers or technologies developed with little understanding of what physicians and patients really need, are also covered. The development of medical technologies is a complex enterprise that requires the integrated expertise of engineers, biologists, physicians, statisticians, and health care administrators. This chapter thus highlights a variety of initiatives that illustrate different approaches to integrate the necessary expertise for innovations that save lives. SUPPORT FOR DISCOVERY RESEARCH IS ADEQUATE Fostering the invention and early stage development of medical technology is essential and depends on the nurturing of basic medical research. Due in no small part to the long-standing and tireless efforts of breast cancer activists, breast cancer research has been generously supported over the past few decades. With the possible exception of AIDS, breast cancer research receives more funding than any other disease. The National Cancer Institute (NCI) currently supports more research projects and clinical trials for breast cancer than for any other type of cancer.51 According to their website, NCI supports 2,932 breast cancer projects and 112 clinical trials. By comparison, the average for all 56 types of cancer (or aspects of cancer) listed by NCI is only 276 projects and 8 clinical trials. In addition to

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis the National Institutes of Health (NIH), breast cancer research is supported by private health charities and the Department of Defense (DoD) Congressionally Directed Medical Research Program, which together provide more than $300 million per year, for a total of roughly $800 million per year (Figure 6-2). By comparison, NCI spent $311 million on prostate cancer and DoD’s Medical Research Program spent $85 million for a total of just under $400 million (Figure 6-3). Table 6-1 lists the major funders of breast cancer research. The Committee believes that current priorities for basic research are appropriate. The investment in basic research over the past few decades has yielded a wealth of knowledge that fuels the invention of a rich array of powerful new technologies from imaging devices that can display the activity of individual cell types to assays that can simultaneously measure the activity of thousands of genes or proteins. A broad consensus among experts in breast cancer over the last few years supports this view. In 1998, the NCI convened the Breast Cancer Research Progress Group, a panel of 30 prominent members of the scientific, medical, and advocacy communities to identify the most important research needs in breast cancer. The panel’s recommendations included research to identify biomarkers, molecular analysis of the transition from pre-invasive to invasive disease, the importance of tissue banks as a critical research resource, the need for biologically based imaging, and the need to develop databases and bioinformatics so that the wealth of data can be FIGURE 6-2 Distribution of public and charitable funding of breast cancer.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis FIGURE 6-3 Percentage of NCI budget allocated to selected cancer types. assimilated and exploited for maximum benefit. Three years later, these same areas were recommended for support in the 2001 Mammography and Beyond report.33 The NCI and DoD breast cancer research portfolios reflect these priorities, as do the research portfolios of key private funders. Further, these same themes have been equally emphasized for all types of cancer. The individual technologies in development for detecting breast cancer are proceeding equally or better than in other disease research areas. Many new technologies hold great promise to improve breast cancer detection. Over the years “breakthroughs” have been announced with great regularity. But there is a long passage between the development of a promising technology and determining whether its promise can be realized. Few of the breakthroughs heralded in past decades have proved their worth in reducing breast cancer mortality. Although the research engine that drives technology advances is well fueled, the validation and implementation of those advances is another matter. Technology Assessment The term “technology assessment” is used in different ways by different people. In the narrowest, but also the most widely used, sense, health technology assessment refers to the synthesis of evidence collected from clinical studies and the application of that synthesis to decisions about whether a particular technology should be adopted by a health care pro-

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis TABLE 6-1 Major Funders of Breast Cancer Research Organization Comments Number of 2001 Grants (grant amount) Type of Organization National Cancer Institute   National cancer program that conducts and supports research, training, health information dissemination, and other programs with respect to cancer patients and family members Overall: 6,397 grants ($2.8 billion) Government Breast cancer: 2,826 grants ($475.2 million) Breast Cancer Research Program (DoD) Promotes research directed toward eradicating breast cancer 378 grants ($175 million) Government Avon Foundation Motivated to benefit women through research, clinical care, support services, education, and early detection, with emphasis on reaching medically underserved women >200 grants ($83 million) Nonprofit Susan G. Komen Foundation Aims to eradicate breast cancer as a life-threatening disease, by advancing research, education, screening and treatment; 90 percent of money raised goes to research 115 grants ($20.4 million) Nonprofit California Breast Cancer Research Program Seeks to reduce the impact of breast cancer in California by supporting research on breast cancer and facilitating the dissemination of research findings and their translation into public health practice 64 grants ($18 million) State government American Cancer Society Dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and service Overall: 84 grants ($46.4 million) Nonprofit Breast Cancer: ($17 million for breast cancer in 2000)

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis Organization Comments Number of 2001 Grants (grant amount) Type of Organization Breast Cancer Research Foundation Dedicated to funding clinical and genetic breast cancer research; 85 percent of the money goes to research 48 grants ($8.5 million) Nonprofit Susan Love MD Breast Cancer Foundation Aims to support the eradication of breast cancer through education, research, and advocacy 12 grants ($110,000) Nonprofit Friends…you can count on Works to educate, promote awareness, raise funds, evaluate promising new projects, and make grants for research for new and improved methods of earlier detection of breast cancer 3 grants ($100,000) Nonprofit Total breast cancer research funding More than $826 million awarded for more than 3,640 grants All funding sources vider or reimbursed by a health care payer, such as a private health insurance company or Medicare. Technology assessment of this sort is conducted by federal and private organizations (Table 6-2). In practice, the initial phase of technology assessment done by health care payers does not usually consider cost, feasibility, or social and ethical issues. The Institute of Medicine (IOM) Committee for Evaluating Medical Technologies in Clinical Use defined medical technology assessment more broadly as: any process of examining and reporting properties of a medical technology used in health care, such as safety, efficacy, feasibility, and indications for use, cost, and cost-effectiveness, as well as social, economic, and ethical consequences, whither intended or unintended.32 Assessing Medical Technologies, IOM, 1985, p. 2 This definition includes clinical studies of efficacy, effectiveness, diagnostic accuracy, the impact of a technology on quality of life, FDA review, and assessment for health insurance coverage, and post-market.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis TABLE 6-2 Federal and Private Technology Assessors FEDERAL ORGANIZATIONS Centers for Medicare & Medicaid Services (CMS) Responsible for tracking emerging technologies and patterns of care to determine applicability of existing national coverage policy and to assess the need for policy change. (Named changed from Health Care Financing Administration, or HCFA, in June 2001.) Medicare Coverage Advisory Committee (MCAC) MCAC advises CMS on whether specific medical items and services are “reasonable and necessary” under Medicare law. MCAC is advisory in nature, with the final decision on all issues resting with CMS. Agency for Healthcare Research and Quality (AHRQ) AHRQ’s Evidence Practice Centers (EPCs) conduct systematic, comprehensive analyses and syntheses of the scientific literature to develop evidence reports and technology assessments on clinical topics that are common, expensive, and present challenges to decisionmakers. U.S. Preventive Services Task Force (USPSTF) Independent panel of preventive health experts, convened by AHRQ, who are charged with evaluating the scientific evidence for the effectiveness of a range of clinical preventive services and producing age-specific and risk factor-specific recommendations for these services. Office of Medical Applications and Research (OMAR) Established in 1977 as part of the NIH Consensus Development program. This is the focal point for evidence-based assessments of medical practice and state-of-the-science on behalf of the medical community and the public. More than 120 NIH Consensus Statements and State-of-the-Science Statements have been issued since the program’s inception. PRIVATE ORGANIZATIONS Blue Cross Blue Shield Association Technology Evaluation Center (BCBSA-TEC) Evaluates the clinical effectiveness and appropriateness of medical procedures, devices, and drugs. The TEC averages 20 to 25 assessments each year, and provides healthcare decision makers, such as Kaiser Permanente and CMS, with information on clinical effectiveness.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis ECRI Nonprofit health services research agency that monitors technology-related hazards, disseminates the results of medical product evaluations and technology assessments, and supplies clinical practice guidelines and standards through several membership-based publications and databases. Hayes, Inc. For-profit technology assessment company that evaluates and monitors emerging health care technologies. Hayes provides assessment information to providers and payers, such as United HealthCare, WellPoint Health Network, and AHRQ. NOTE: For the purposes of this table, technology assessment is defined as the synthesis of clinical evidence concerning medical technologies for making coverage decisions and developing clinical guidelines. Assessments of how well a technology is implemented in clinical practice or how it is most effectively integrated with existing technologies are rarely conducted. (Post-market surveillance studies assess product failures as opposed to optimizing performance.) In other words, how effectively a new technology improves overall health outcomes is rarely studied. Medical technology assessment in the United States has been described as “a battle that’s been fought and lost many times before”29 (Box 6-1). Although national advisory panels have called for a nationally coordinated system of health technology assessment for decades,32 no federal agency in the United States has both the mandate and the power to support a comprehensive approach to technology assessment. The mission statement of the Agency for Healthcare Research and Quality (AHRQ) includes technology assessment, but that agency has never been allocated enough funds to support comprehensive technology assessment. The NIH budget is more than 100 times greater than AHRQ’s, but its mandate for technology assessment is limited to clinical trials and NIH has historically resisted further expansion in that direction. In coming years, the gap between technology innovation and assessment might begin to narrow. In May 2002, the NIH director, Elias Zerhouni, laid out the “NIH Roadmap” describing a strategic vision for a more integrated approach to basic research that enables technological innovation and technology development. The Roadmap is discussed later in this chapter.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis BOX 6-1 Brief History of Medical Technology Assessment in the U.S. Federal Government21 1972 Office of Technology Assessment (OTA) was created in 1972 as an analytical arm of Congress and conducted studies in nine areas, one of which was health. 1977 NIH Consensus Development Program was established as a mechanism to judge—in an unbiased, impartial manner—controversial topics in medicine and public health. NIH has conducted 115 consensus development conferences, and 22 state-of-the-science (formerly “technology assessment”) conferences, addressing a wide range of issues. 1978 Office of Medical Applications of Research (OMAR) was established as part of the NIH Consensus Development Program. This is the focal point for evidence-based assessments of medical practice and state-of-the-science on behalf of the medical community and the public. NIH resisted the establishment of this office for many years, but eventually could no longer resist congressional pressure. 1978 National Center for Healthcare Technology was established to advise the Health Care Financing Administration (HCFA, now CMS) on coverage decisions for new medical technologies under the Medicare program. 1981 National Center for Health Care Technology (NCHCT) was eliminated. The American Medical Association (AMA) and Health Industry Manufacturers Association (HIMA) (now known as AdvaMed), led the move. However, the center paved the way for the AHRQ. 1981 Office of Health Technology Assessment (OHTA) of the National Center for Health Services Research assumed the responsibilities of NCHCT following its elimination. 1995 OTA was not funded by Congress during a time of budgetary concerns. 1999 American College of Radiology Network (ACRIN) is the first large-scale collaborative clinical trials group devoted to the development of technologies for medical imaging. Clinical trials were launched in 1999. 2001 National Institute of Biomedical Imaging and Bioengineering (NIBIB) was established. The NIBIB mission statement includes the “translation and assessment of technological capabilities in biomedical imaging…” This is the first NIH institute to include technology assessment in its mission statement. 2003 Intense debate over the value of the AHRQ, the only “official” federal medical technology assessment agency. Some lawmakers were in favor of closing the agency. The AHRQ budget, which was already too small to allow anything beyond very limited funding of clinical technology assessment, was reduced. AHRQ was reauthorized only until 2005.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis The Role of Cost-Effectiveness Analysis As noted above, cost-effectiveness is rarely assessed in the initial phase of technology assessment done by health care payers. Nor is it part of FDA’s approval criteria. The Committee agrees that this is appropriate, because it makes little sense to assess cost-effectiveness analysis before effectiveness is determined. Likewise, it is premature to be overly concerned about cost-effectiveness during research and development of new technologies. Besides lacking information about the effectiveness of technologies that have not been clinically tested, later generations of a technology are almost always less expensive and often more effective.60 Consideration of cost-effectiveness is important during the technology adoption process, but at this stage formal cost-effectiveness analysis is seldom undertaken and generally does not play a role in the decision to adopt a new technology. As technology diffuses, or is poised for diffusion, cost effectiveness, or perceptions of it, influence policymaker’s views and the decisions of insurers and health care systems about whether to recommend or use a technology. Cost-effectiveness analysis has the potential to contribute to rational decision making by providing estimates of the magnitude of costs and health outcomes. When conducted in an unbiased way, it can help with decisions about whether or not to recommend a technology in different subgroups (such as screening of men for breast cancer) and with choices between alternative interventions for the same group (for example, screening women for breast cancer versus recommending the use of a drug that has been shown to prevent breast cancer). Cost-effective analysis also can be used to choose between alternative strategies to achieve some overall societal or population goal; for example, in choosing whether to implement a screening program for breast cancer versus a screening program for ovarian cancer to reduce the burden of cancer in women. Cost-effectiveness analysis is not and should not be the only consideration in decisions about technology use. Cost-effectiveness analysis does not address value judgments that are key to individuals making decisions about their health. Cost-effectiveness analysis is influenced by perspective—that is, whose benefits, costs, and burdens are “counted” and are thus included in the analysis, and whether to count all benefits, burdens, and cost that accrue to certain individuals or groups.27 For example, patients, physicians, health plans, and insurers have different perspectives and will likely weigh costs and benefits differently. A decision to adopt a new technology because it is “worth the cost” is an ethical and moral judgment—not an economic one. Opinions about whether something is “worth” a certain amount of money are subject to differences in the perspective and values of those making the judgment.55

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis METHODOLOGICAL ISSUES Clinical studies are one of the first steps in assessing medical technologies. Unfortunately, far too many clinical studies yield uninformative data and fail to answer the basic question as to whether a new technology improves health outcomes. Too often, the appearance of a positive result is an illusion based on overlooked assumptions and failures to appreciate the many ways that hidden biases can skew results (Box 6-2). Poor Study Designs Impede Progress The consequences are disheartening. The developer of a new technology has typically invested millions of dollars in a clinical study—not to mention the time and effort of participating physicians, nurses, and patients. The ability to fund a clinical study is often a limiting factor for a small company hoping to develop a promising medical technology. From a company’s perspective, failure to obtain FDA approval spells disaster, and often signals the end of the project. Small companies whose fortunes are tied to a single technology and who rely on venture capital will find it considerably more difficult—if not impossible—to raise further capital, which often leads to the demise of the company. Ultimately, it is the patients who suffer most from these lost opportunities. BOX 6-2 Common Failures in Clinical Trial Designs Submitted for Review (See Appendix D for Detailed Descriptions) Poorly Described Patient Populations Too Narrow a Patient Population Failure to Use Appropriate Controls or Comparison Groups Failure to Demonstrate the Comparability of Patients in Treatment and Control Groups Unclear Definition of Study Endpoints Bias Confounding Systematic Errors or Differences in Measurement Loss of Patients to Follow-Up Inappropriate Statistical Analysis and Planning Poorly Described Techniques

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis BOX 6-9 Reengineering the Clinical Research Enterprise Over the years, clinical research has become more difficult to conduct. However, the exciting basic science discoveries currently being made demand that clinical research continue and even expand. This is undoubtedly the most difficult but most important challenge identified by the NIH Roadmap process. The United States must recast its entire system of clinical research if efforts to fight disease are to remain as successful as they have been in the past. The NIH Roadmap will promote the creation of better integrated networks of academic centers that work jointly on clinical trials and that include community-based physicians who care for sufficiently large groups of well-characterized patients. Implementing this vision will require new ways to organize the way clinical research information is recorded, new standards for clinical research protocols, modern information technology, new models of cooperation between NIH and patient advocacy alliances, and new strategies to reenergize the clinical research workforce. Translational research. Scientists have become increasingly aware that the bench-to-bedside approach to translational research is really a two-way street. Not only do basic scientists deliver to clinicians new tools to examine patients, but clinical researchers also make novel observations about the nature and progression of disease that can stimulate basic investigations. Translational research is a powerful process that primes the entire clinical research engine, but this component of the clinical research enterprise should be optimized and accelerated through a stronger infrastructure. NIH is exploring development of regional translational research centers. These centers would provide sophisticated advice and resources to better enable scientists to master the many steps involved in bringing a new product from the bench to clinical use. Clinical workforce training. Our nation’s ability to fully explore the ever-expanding opportunities for medical advances is limited only by our resources, the most important of which is the scientific workforce. To fulfill the promise of 21st century medicine and to make further progress in controlling major human diseases, we must cultivate and train a cadre of clinical researchers with skills commensurate with the increasing complexity and needs of the research enterprise. The NIH Roadmap effort envisions two major programs to expand, enhance, and empower the clinical research workforce: the establishment of an agency- of whom have little experience with regulatory processes and often founder as a result—to help avoid wasting time and money in what is normally a long and expensive process. The Council provides advice to medical technology developers on the spectrum of scientific, regulatory, and reimbursement issues related to developing an imaging device or technology. Any business or academic investigator developing a device or technology relevant to biomedical imaging in

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis wide Multidisciplinary Clinical Research Workforce Training Program and a cadre of NIH Clinical Research Associates. Clinical research networks. An enriched pipeline of biomedical discoveries, an infrastructure to facilitate their translation from the lab to the clinic, and a robust force of clinical investigators will make it possible to test new detection and diagnostic strategies in larger numbers of patients far sooner than at present. These large studies are often best conducted through networks of investigators who are equipped with tools to facilitate collaboration and information sharing. Because of the vast number of procedures and technologies that must be evaluated through clinical trials, many clinical research networks operate simultaneously, but independently of each other. As a result, researchers must sometimes duplicate already existing data because they are unaware the data exist or they cannot access them. Standardizing data reporting would enable seamless data and sample sharing across studies. Reduced duplication of studies will leave more time and funds to address additional research questions. A blueprint for a national informatics network using standardized data, software tools, and network infrastructure will evolve from an inventory of existing clinical research networks. Other impediments to efficient clinical research to be addressed through this set of initiatives are the multiple requirements of diverse regulatory and policy agencies. Researchers face a tremendous diversity of requirements in reporting adverse events to NIH, the FDA, the Office of Human Research Protections, and institutional review boards, among others. Clinical researchers must understand and fulfill these varying requirements that often overlap and might even contradict one another. NIH aims to take a leadership role in working with other agencies to develop better processes and to standardize requirements for reporting adverse events, human subjects protections, privacy and conflict-of-interest policies, and standards for electronic data submission. Harmonizing policies and reporting requirements will help minimize unnecessary burdens that slow research, while at the same time enhancing patient protections. By standardizing the regulatory requirements of clinical research networks and enhancing their interoperability, clinical research will advance more swiftly, and more and better therapies will reach patients nationwide. By creating a partnership with patients and physicians—true “communities of research”—this ambitious set of NIH Roadmap initiatives promises to enhance the scope, resilience, efficiency, and impact of the nation’s clinical research workforce, ultimately improving the health of all Americans. SOURCE: See http://nihroadmap.nih.gov/clinicalresearch. Accessed March 1, 2004.47 cancer may submit a request to make a presentation, and small businesses are particularly encouraged to apply. A presenter typically meets with the Council for an informal, confidential discussion with emphasis on helping the presenter develop an effective approach for FDA approval and streamlining the process of coverage and reimbursement decisions from CMS. The Council hosts an annual conference on biomedical imaging in oncology, designed to identify areas of new biomedical opportunity and

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis address challenges in the cancer imaging community, focusing on the regulatory, coverage, and reimbursement issues associated with more developed and established technologies. FDA and CMS coordination of their discussions of new technologies is another value of ICBIO, with the potential of easing an oft-cited bottleneck to technology development. Developers of early stage medical technology have long commented that the process of FDA and CMS review are so unpredictable and burdensome that they unduly impede the development of innovation technologies.33 ICBIO is one example of the series of proactive strategies that federal agencies have taken in recent years to address these problems. National Digital Mammography Archive As digital imaging technology becomes increasingly cost-effective, mammography is expected to move away from a film-based format. This transition will also increase opportunities for electronic sharing of images, data, and other information among a wide network of clinicians and researchers. To this end, researchers at the Universiy of Pennsylvania, along with collaborators at the Universities of Chicago, North Carolina, and Toronto and contractors at Oak Ridge National Laboratory in Tennessee, have assembled and tested a prototype for a national database, the NDMA.1 Mammography services could be greatly streamlined if breast imagers were able to examine mammographic images stored at multiple sites from their own facility. This would eliminate the need to physically transfer mammograms from site to site, and would go a long way toward ending the all too common frustration and delays caused by lost mammograms. This project tests the computer’s ability to store and instantly retrieve vast numbers of high-quality digital mammograms from distant sites. Medical image data is different from other types of data because the file sizes are large (hundreds of megabytes per exam) and the required turn-around time is short. The NDMA system exploits the speedy content-delivery capabilities of Internet2, which has made it feasible to transfer large quantities of medical image data over low-cost and high-speed wide-area networks. Cumbersome files will no longer have to be mailed in hard-copy format. The NDMA can also facilitate consultation and collaboration among physicians on difficult cases, particularly when they occur in underserved areas. For example, researchers at the University of Toronto are using a mobile van to download mammograms in remote locations.45 These functions may be further enhanced by the planned development of the NDMA as a central resource for computer-aided diagnosis. InfoWorld, a media group that specializes in information technologies, recognized the NDMA

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis in 2002 as the #1 project that best exemplifies the implementation of innovative technology. Initiated in 2000 with a 3-year grant from the National Library of Medicine’s Next Generation Internet initiative, the NDMA project went live in 2002 at the four participating institutions (Figure 6-4). The pilot archive, comprising digital images and information, can be accessed through web portals at each of the four institutions. With continued funding, the network is expected to expand gradually to connect approximately 2,000 mammography facilities.45 This will be accomplished through the construction of a few large regional archives distributed across the country, linked to smaller, more local archives that store data collected within 2 to 3 years, which in turn serve individual hospitals, universities, and other health care institutions through secure portals that can both send and receive information. Currently, a single area archive connects all of the participating institutions. During the first 3 years of the project, researchers enrolled about 10 patients per day, uploading their mammography data to the NDMA.68 Archived images are primarily derived from digital mammograms; films also have been digitally scanned for inclusion in the archive, but produced FIGURE 6-4 Architecture of the National Digital Mammography Archive (NDMA). Courtesy of Dr. Mitchell Schnall and Pat Payne.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis lower-quality images.45 Mammography reports, conforming to BI-RADS® guidelines, are also posted to the archive. In additional to digital mammography, the NDMA can store MRI, ultrasound, and other imaging formats that conform to the binary standard known as Digital Imaging and Communications in Medicine. The expanded capabilities of the Internet2, also known as Next Generation Internet, are essential to the efficient storage, retrieval, and security of mammography information. Indeed, devising a means of storing enormous quantities of data was one of the most significant challenges. Unlike the standard Internet, the bandwidth and technology of Internet2 can accommodate the storage of very large digital image files—which are predicted to exceed capacity for management and storage by breast center sites—and enable their instant transfer across the network.1 The use of grid-computing addresses is “the trick of making use of digital images, indexing them, and delivering them to hospital locations on demand,” says Robert Hollebeek, chief architect of the NDMA. The Internet2 “grid” framework is also key to ensuring patient privacy and confidentiality, as required by the HIPAA Privacy Rule. Multiple levels of system security include access control, encryption, and the use of virtual private networks, as well as confidentiality safeguards for research purposes that strip personal information that could be used to identify individual patients. With these safeguards in place, the NDMA constitutes a rich reserve of data that can be “mined” for research and education. Epidemiologists could, for example, use the database to compare breast cancer incidence and prevalence among women of various ages or ethnicities, or in different areas of the country. A national teaching file is being developed as part of the NDMA project to provide teaching and testing material for mammography training programs.1,68 Currently, teaching cases for the training of radiologists and mammographers tend to be developed separately at individual institutions, and this limits students’ exposure to cases that occur in that medical center. Some day, radiologists may be able to annotate mammogram images with specific location data and upload them to the NDMA for inclusion in cases file for teaching, testing, and advanced training.48 In the future, the NDMA could link to similar databases under development in the United Kingdom, France, Germany, and Japan to create an international mammography archive.31 The U.K. project, which is jointly funded by that nation’s government and IBM, resembles the NDMA in size, scope, and design. These expanded, global networks offer the potential of even greater opportunities for research, education, and the efficient exchange of patient information.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis Technology Assessment Centers for Breast Cancer Detection In contrast to the relative wealth of resources for discovery research, there are very limited resources devoted to the clinical testing of new technologies for breast cancer detection. Companies developing new technologies often hire academic investigators to run their FDA trials. These trials tend to have limited aims—to prove the safety and efficacy of the new products for purpose of marketing and selling the new product. FDA approval does not require assessment of utility of a new technology in clinical practice. The real clinical utility of a new technology depends on how it will be used or co-used with other tests and on which population of women at risk for breast cancer. The specificity, sensitivity, and diagnostic accuracy all vary with the clinical question being addressed and the population being tested. So, while a device may meet FDA’s requirements for marketing, deciding whether the device adds value to their decision-making process or merely adds cost is a more complicated question to physicians and their patients. Unfortunately, because little clinical testing of devices is done after the FDA approval process, the adoption of new technologies by users such as radiologists too often depends more on marketing hype and the need to be perceived as having the latest and greatest new products than by clear evidence as to whether those products are really useful to patients. Currently, very few clinical trials are funded annually to determine whether new technologies might improve the detection and/or diagnosis of breast cancer. Such trials require access to patient populations willing to undergo extra experimental tests, as well as a cadre of investigators who are skilled in trial design and execution. As a rule, academic medical centers do not consider the clinical testing of new technologies to be part of their mission. Multicenter, collaborative studies offer an effective way to meet the need for timely and generalizable clinical evaluations of imaging technologies.26 The NIH uses many criteria in determining the need to establish specific research center programs, but certain criteria are applied across the board, each of which applies to centers for research on developing, assessing, and implementing new technologies for breast cancer detection (Box 6-10).34 The model of Comprehensive Cancer Centers and their utility in testing new drug therapies could be applied to the testing of new technologies. Centralized resources where imaging experts, including scientists who can adapt a technology to a new clinical problem, patients willing to participate in clinical trials, and an institution whose mission includes the application and testing of new technologies would provide an infrastructure that would allow new devices to become tested and available to those who need them much more systematically (and quickly) than the system that is currently

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis BOX 6-10 NIH Criteria for Establishing Center Programs The scientific opportunities and/or public health needs that the program would address have high priority. The center would provide an organizational environment that would facilitate activities that are most effectively undertaken by teams of investigators working in close proximity. The activities include: Multidisciplinary collaborations for problems that require diverse scientific backgrounds. Multi-investigator teams capable of a scope of activities not possible with other funding mechanisms. Translating the results of basic research into clinical practice. Complementing existing and stimulating new investigator-initiated applications for research project grants. Training of graduate students, postdoctoral fellows, physician-scientists, nurses, and other health professionals in cross-disciplinary or translational research. Attracting experienced researchers into a new area of research. Networking with other centers in the program to conduct coordinated research beyond the capacity of any single center. The centers would provide critical research resources needed for productive research that are difficult or too expensive to develop in most individual laboratories. The centers would build the infrastructure to promote the institutional development of a field of research. available. In addition, other endpoints besides diagnostic accuracy, such as cost effectiveness and quality of life, could also be centrally and more uniformly studied in such centers. REFERENCES 1. National Digital Mammography Archive. 2001, May 1. Web Page. Available at: http://nscp01.physics.upenn.edu/NDMA/ndma.html. 2. AcademyHealth. 2003. Playing by New Rules: Privacy and Health Services Research. Background paper for the April 29, 2003. Workshop Playing by New Rules: Privacy and Health Services Research. 3. AdvaMed. 2003, August 5. AdvaMed Commends FDA Commisioner’s Plan to Speed Review Times; Effort to Complement MDUFMA Performance Goals. Web Page. Available at: http://www.advamed.org/publicdocs/PR-188.htm. 4. AdvaMed. 2004, February 20. AdvaMed Welcomes President Bush’s Announcement to Nominate Mark McClellan as New CMS Administrator. Web Page. Available at: http://www.advamed.org/publicdocs/PR-203.htm.

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Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis 5. Advani AS, Atkeson B, Brown CL, Peterson BL, Fish L, Johnson JL, Gockerman JP, Gautier M. 2003. Barriers to the participation of African-American patients with cancer in clinical trials: a pilot study. Cancer 97(6):1499-1506. 6. Agency for Healthcare Research and Quality. 2001. Diagnosis and Management of Specific Breast Abnormalities. Summary, Evidence Report/Technology Assessment. AHRQ Publication No. 01-E045. Rockville, MD: Agency for Healthcare Research and Quality. 7. American College of Radiology Imaging Network (ACRIN). 2004. ACRIN—Frequently Asked Questions. Accessed March 4, 2004. Web Page. Available at: http://www.acrin.org/faq.html#current. 8. American College of Radiology Imaging Network (ACRIN). 2004. Digital Mammographic Imaging Screening Trial (DMIST). Accessed March 4, 2004. Web Page. Available at: http://www.dmist.org. 9. American Heart Association. 2001. Heart Disease and Stroke Statistics—2002 Update. Dallas, TX: American Heart Association. 10. Association of American Medical Colleges. 2003. Group on Institutional Advancement. Accessed April 4, 2003. Web Page. Available at: http://www.aamc.org/members/gia/start.htm. 11. Blue Cross Blue Shield Association Technology Evaluation Center. 2003. Full Field Digital Mammography. Tec Assessment Program 17(7):1-22. 12. Bole K, Bio-IT World. 2003. Decoding HIPAA: Are You Ready? Accessed February 2003. Web Page. Available at: http://www.bio-itworld.com/archive/030702/hippa.html. 13. Bonetta L, Dove A, Watanabe M. 2003. The road to research is paved with restrictions. Nat Med 9(6):630. 14. CenterWatch. 2003. Projecting HIPAA’s Impact. CenterWatch Newsletter 10(5). 15. CenterWatch. 2002. Breaking the development speed barrier. CenterWatch Newsletter 9(6). 16. Cho MK, Sankar P, Wolpe PR, Godmilow L. 1999. Commercialization of BRCA1/2 testing: practitioner awareness and use of a new genetic test. Am J Med Genet 83(3):157-163. 17. Collins FS, Watson JD. 2003. Genetic discrimination: time to act. Science 302(5646):745. 18. Corbie-Smith G, Ammerman AS, Katz ML, St Georg DM, Blumenthal C, Washington C, Weathers B, Keyserling TC, Switzer B. 2003. Trust, benefit, satisfaction, and burden: a randomized controlled trial to reduce cancer risk through African-American churches. J Gen Intern Med 18(7):531-541. 19. Cox K, McGarry J. 2003. Why patients don’t take part in cancer clinical trials: an overview of the literature. Eur J Cancer Care (Engl) 12(2):114-122. 20. Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System Online Prevalence Data. 1995. Accessed June 1, 2004. Web Page. Available at: http://apps.nccd.cdc.gov/brfss/age.asp?cat=HC&yr=2000&qkey=4341&state=US. 21. Eisenberg J, Zarin D. 2002. Health technology assessment in the United States: Past, present, and future. Int J Technol Assess Health Care 18(2):192-198. 22. Feigal D. 2003. Challenges in Assessing the Safety and Efficacy of Cancer Detection Devices. Institute of Medicine Workshop: From Development to Adoption of New Approaches to Breast Cancer Detection and Diagnosis. Washington, DC: The Institute of Medicine of the National Academies.

OCR for page 188
Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis 23. Fisher ES, Wennberg DE, Stukel TA, Gottlieb DJ, Lucas FL, Pinder EL. 2003. The implications of regional variations in Medicare spending. Part 2: health outcomes and satisfaction with care. Ann Intern Med 138(4):288-298. 24. Fisher ES, Wennberg DE, Stukel TA, Gottlieb DJ, Lucas FL, Pinder EL. 2003. The implications of regional variations in Medicare spending. Part 1: the content, quality, and accessibility of care. Ann Intern Med 138(4):273-287. 25. Gammon MD, Neugut AI, Santella RM, Teitelbaum SL, Britton JA, Terry MB, Eng SM, Wolff MS, Stellman SD, Kabat GC, Levin B, Bradlow HL, Hatch M, Beyea J, Camann D, Trent M, Senie RT, Garbowski GC, Maffeo C, Montalvan P, Berkowitz GS, Kemeny M, Citron M, Schnabe F, Schuss A, Hajdu S, Vincguerra V, Collman GW, Obrams GI. 2002. The Long Island Breast Cancer Study Project: description of a multi-institutional collaboration to identify environmental risk factors for breast cancer. Breast Cancer Res Treat 74(3):235-254. 26. Gatsonis C, McNeil BJ. 1990. Collaborative evaluations of diagnostic tests: experience of the Radiology Diagnostic Oncology Group. Radiology 175(2):571-575. 27. Goold SD, Vijan S. 1998. Normative issues in cost effectiveness analysis. J Lab Clin Med 132(5):376-382. 28. Hadley DW, Jenkins J, Dimond E, Nakahara K, Grogan L, Liewehr DJ, Steinberg SM, Kirsch I. 2003. Genetic counseling and testing in families with hereditary nonpolyposis colorectal cancer. Arch Intern Med 163(5):573-582. 29. Health Care Information Center. 2002. Medicine and Health 58(38). 30. Hillman BJ, Schnall MD. 2003. American College of Radiology Imaging Network: future clinical trials. Radiology 227(3):631-632. 31. IBM News-Australia. 2002, October 14. Oxford University, IBM and UK Government to build massive computing grid for breast cancer screening and diagnosis. Accessed August 21, 2003. Web Page. Available at: http://www.ibm.com/news/au/2002/10/2002102201.html. 32. Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: National Academy Press. 33. Institute of Medicine. 2001. Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer. Washington, DC: National Academy Press. 34. Institute of Medicine. 2004. NIH Extramural Center Programs: Criteria for Initiation and Evaluation. Washington, DC: The National Academies Press. 35. Kaiser Family Foundation. 2002. State Mandated Benefits: Contraceptives. Accessed July 27, 2003. Web Page. Available at: http://www.statehealthfacts.kff.org/cgi-bin/healthfacts.cgi?action=compare&category=Women%27s+Health&subcategory=Mandated+Benefits%3a+Private+Insurers&topic=Contraceptives. 36. Klabunde C, Kaluzny A, Ford L. 1995. Community Clinical Oncology Program participation in the Breast Cancer Prevention Trial: factors affecting accrual. Cancer Epidemiol Biomarkers Prev 4(7):783-799. 37. Kramer BS, Gohagan JK, Prorok PC. 1990. Cancer Screening: Theory and Practice. New York: Marcel Dekker. 38. Lara PN Jr, Higdon R, Lim N, Kwan K, Tanaka M, Lau DH, Wun T, Welborn J, Meyers FJ, Christensen S, O’Donnell R, Richman C, Scudder SA, Tuscano J, Gandara DR, Lam KS. 2001. Prospective evaluation of cancer clinical trial accrual patterns: identifying potential barriers to enrollment. J Clin Oncol 19(6):1728-1733. 39. Marsden J, Bradburn J. 2004. Patient and clinician collaboration in the design of a national randomized breast cancer trial. Health Expect 7(1):6-17. 40. McClellan MB, Commissioner of Food and Drugs. 2003. Technology and innovation: their effects on cost growth of healthcare. Joint Economic Committee. 41. McCormack J. 2003. ALLHAT—so what? J Inform Pharmacother (12).

OCR for page 188
Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis 42. Messerli FH. 2001. Doxazosin and congestive heart failure. J Am Coll Cardiol 38(5):1295-1296. 43. Michaelson JS, Silverstein M, Wyatt J, Weber G, Moore R, Halpern E, Kopans DB, Hughes K. 2002. Predicting the survival of patients with breast carcinoma using tumor size. Cancer 9(4):713-723. 44. Mouton CP, Harris S, Rovi S, Solorzano P, Johnson MS. 1997. Barriers to black women’s participation in cancer clinical trials. J Natl Med Assoc 89(11):721-727. 45. Murray W. 2002. Cancer’s new enemy. New Architect 7:10-12. 46. National Cancer Institute. FY2003 Bypass Budget. 2001. Plans & Priorities for Cancer Research: The Nation’s Investment in Cancer Research for Fiscal Year 2003. Bethesda, MD: National Cancer Institute. 47. National Cancer Institute. 2003. Summary, Fourth National Forum on Biomedical Imaging in Oncology. Accessed August 21, 2003. Web Page. Available at: http://cancer.gov/dctd/forum/summary03.pdf. 48. National Cancer Institute. 2003. Fourth National Forum on Biomedical Imaging in Oncology Meeting Summary. Bethesda, MD: National Cancer Institute. 49. National Cancer Institute. 2003. Understanding the Approval Process of New Cancer Treatments: A Short History. Accessed July 27, 2003. Web Page. Available at: http://www.nci.nih.gov/clinicaltrials/understanding/approval-process-for-cancer-drugs/page6. 50. National Cancer Institute. 2003. caBIG at a Glance: Overview of Activities and Accomplishments to Date. Accessed August 27, 2003. Web Page. Available at: http://cabig.nci.nih.gov/overview. 51. National Cancer Institute. 2004. Cancer Research Portfolio. Accessed February 23, 2004. Web Page. Available at: http://researchportfolio.cancer.gov/cgi-bin/search.pl?Search=cancer&x=47&y=13. 52. National Institutes of Health. 2003. Protecting Personal Health Information in Research: Understanding the HIPAA Privacy Rule. Bethesda, MD: National Institutes of Health, Department of Health and Human Services. 53. National Institutes of Health. 2004. Re-engineering the Clinical Research Enterprise. Accessed February 20, 2004. Web Page. Available at: http://nihroadmap.nih.gov/clinicalresearch. 54. Paskett ED, Cooper MR, Stark N, Ricketts TC, Tropman S, Hatzell T, Aldrich T, Atkins J. 2002. Clinical trial enrollment of rural patients with cancer. Cancer Practice 10(1):28-35. 55. Petitti DB. 2000. Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis. 2nd ed. New York: Oxford University Press. 56. Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA. 2002. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359(9306):572-577. 57. Pisano ED. 2000. Current status of full-field digital mammography. Radiology 214(1):26-28. 58. Pressel S, Davis BR, Louis GT, Whelton P, Adrogue H, Egan D, Farber M, Payne G, Probstfield J, Ward H. 2001. Participant recruitment in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Control Clin Trials 22(6):674-686. 59. Rao PN, Levine E, Myers MO, Prakash V, Watson J, Stolier A, Kopicko JJ, Kissinger P, Raj SG, Raj MH. 1999. Elevation of serum riboflavin carrier protein in breast cancer. Cancer Epidemiol Biomarkers Prev 8(11):985-990. 60. Rogers EM. 1995. Diffusion of Innovations. 4th ed. New York: Free Press.

OCR for page 188
Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis 61. Rosenberg A. 2003. Private Payers’ Perspectives on Adoption of New Breast Cancer Detection Technologies. Institute of Medicine Workshop: From Development to Adoption of New Approaches to Breast Cancer Detection and Diagnosis. 62. Sateren WB, Trimble EL, Abrams J, Brawley O, Breen N, Ford L, McCabe M, Kaplan R, Smith M, Ungerleider R, Christian MC. 2002. How sociodemographics, presence of oncology specialists, and hospital cancer programs affect accrual to cancer treatment trials. J Clin Oncol 20(8):2109-2117. 63. Sung NS, Crowley WF Jr, Genel M, Salber P, Sandy L, Sherwood LM, Johnson SB, Catanese V, Tilson H, Getz K, Larson EL, Scheinberg D, Reece EA, Slavkin H, Dobs A, Grebb J, Martinez RA, Korn A, Rimoin D. 2003. Central challenges facing the national clinical research enterprise. JAMA 289(10):1278-1287. 64. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 2002. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288(23):2981-2997. 65. Tunis S. 2003. CMS Perspectives on Adoption of New Breast Cancer Detection Technologies. Institute of Medicine Workshop: From Development to Adoption of New Approaches to Breast Cancer Detection and Diagnosis. Washington DC: Institute of Medicine. 66. U.S. Food and Drug Administration. 1998. Overview—FDA Modernization Act of 1997. Web Page. Available at: http://www.fda.gov/cdrh/devadvice/371.html. P. 4. 67. U.S. Food and Drug Administration. 2003. Improving Innovation in Medical Technology: Beyond 2002. Rockville, MD: U.S. Food and Drug Administration. 68. UNC Lineberger Comprehensive Cancer Center. 2003. Research Resources: Etta D. Pisano, MD. Web Page. Available at: http://cancer.med.unc.edu/researchers/DisplayByList.asp?ID=142. 69. Wagner L. 2004. A test before its time? FDA stalls distribution process of proteomic test. J Natl Cancer Inst 96(7):500-501. 70. Wang JG, Staessen JA, Heagerty AM. 2003. Ongoing trials: what should we expect after ALLHAT? Curr Hypertens Rep 5(4):340-345. 71. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. 2003. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 3(1):25. 72. Winslow R, Hensley S. 2002, December 18. Dose of reality: study questions high cost of drugs for hypertension. The Wall Street Journal.