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Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2 (2000)

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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2

IOM Committee on the Early Detection of Breast Cancer:

Second Workshop, June 19–20, 2000

INTRODUCTION

In November 1999, the Institute of Medicine, in consultation with the Commission on Life Sciences, the Commission on Physical Sciences, Mathematics, and Applications, and the Board of Science, Technology and Economic Policy initiated a one-year technology assessment study on emerging technologies for the early detection of breast cancer. The committee's mandate was twofold: (1) to review emerging technologies that could potentially aid in earlier detection of breast cancer and (2) to recommend priorities for bolstering the technology development, evaluation, and adoption process, with the goal that such development could reduce breast cancer burden and deaths. As part of its charge, the committee held two workshops. At the first public workshop, held in February 2000, outside experts were invited to describe a variety of promising emerging early detection technologies. A second workshop, held June 19-20, 2000, examined several factors that influence whether or not a new cancer detection technology is developed, tested, and enters the clinic; how fast the technology development process proceeds; the key players in the technology development process; and the current climate for technology development.

As described at the first workshop, many new and improved technologies are being studied for the early detection of breast cancer, but many barriers must be overcome during the process of development, assessment, and dissemination. The expert presentations at the second

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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workshop, as summarized here, described many important influences on the development and adoption process.

NIH Support for New Technologies*

The National Cancer Institute has been actively developing programs to make the National Institutes of Health peer review system more accessible and friendly to technology development. According to Carol Dahl, “one problem that NCI has been struggling with is that the traditional NIH peer review system has not necessarily been friendly to non-hypothesis driven research.” The National Institutes of Health Center for Scientific Review and Office of External Research has taken a very proactive stance in tutoring the study sections that look at these applications. In addition, NCI established a new Office of Technology and Industrial Relations two years ago to facilitate expedited technology development and transfer activities.

Aiming to develop a more streamlined grant application and award process for technology discovery and development, the National Cancer Institute has held several meetings with the research community. These discussions have proved fruitful and have revealed that traditional grant awards for technology development do not mesh well with the uncertain timetable of technology discovery, development, and adoption.

In FY 2000, NCI invested $63.7 billion in Small Business Innovative Research (SBIR) awards and another $3.8 million in Small Business Technology Transfer Research (STTR) grants.

*

Based on a presentation by Carol Dahl, Director, Office of Technologies and Industrial Relations, National Institutes of Health

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Technology development initiatives

Recently launched initiatives allow for more flexibility in timing and dollar allocations. As the initiatives have been better tailored to accommodate the needs of investigators, the quality of recent grant applications has gone up substantially, according to Dahl. More focused initiatives target understanding the fundamental nature of cancer and offer researchers “extraordinary opportunities in FY 2001,” according to Dahl. Areas of focus include genes and the environment, cancer imaging, defining the signatures of cancer tumors, molecular targets of prevention and treatment, tobacco and related cancers, and cancer communications. However, the enhanced flexibility in time and dollar allocations has also made it harder for NCI to meet its commitments.

Recognizing that the fundamental nature of cancer is genetic, these NCI initiatives focus on the impact of those genetic changes on the expressed products of the genome, including the RNA, the proteins, and the protein interactions that create the functional networks themselves. Of particular interest to NCI are technologies that will permit evaluating multiple levels of analysis: the in vitro (test tube) level, in situ (cellular) level, and in vivo (whole body) level. The Institute is also backing the development of modeling tools, as well as supporting work on the discovery phase - determining the tumor's molecular signature. As the Institute envisages this work, it hopes that emerging technologies will provide the tools for molecular detection, diagnosis, and also facilitate finding new targets for interventions as well.

Phased Innovation Award

The Phased Innovation Award is a new mechanism directed at supporting technology research from the evolution of the innovative concept to the research development phase.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

Compared with the traditional R21 grant application process, which awards funding in a two-step process and has proved cumbersome in furthering technology development, the Phased Innovation Award allows for a single submission of two previously distinct awards (the R21 [proof of concept phase]) and the R33.

The Phased Innovation Award couples the two awards into one. To move into the second phase, investigators must achieve measurable milestones. Advantages of the new award are that it can be expedited through an administrative review, it eliminates the resubmission of a grant and forces investigators to think toward the future.

In considering awards for detection technologies, drug discovery, the award permits flexible staging for research up to four years. Additionally, there is an ongoing open window for grant awards, with three receipt days yearly. According to Dahl, the molecular analysis community has responded enthusiastically to the program and she predicts considerable program expansion.

Annual expenditures for the program approximate $12 million, with an additional $23 million expended in small business awards. Additionally, the Phased Innovation Award is beginning to be used as a funding model across the National Institutes of Health.

Technology development on the molecular analysis of cancer

The Institute has also created an additional mechanism to bolster study for molecular analysis awards that enables researchers to expedite studying the utility of a novel technology on sample type of interest to the investigator. Under the first phase, the investigator must show proof of concept in a pilot biological application and then can generate the data that would permit continuing on to the next phase. The feasibility stage (formerly the R21) can extend up to two years; the R33 can last between one to three years. This mechanism provides funding for a maximum of four years, enables a parallel solicitation in the business community, and grant

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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applicants can apply on three calendar dates per year. So far, this grant mechanism has proved very popular in the biotechnology community.

Cancer imaging

The National Cancer Institute is also pursuing enhancing opportunities that bring the molecular world together with the imaging community, with the goal of identifying the fundamental molecular signature of tumors. Several program announcements address this area, including developmental grants for diagnostic cancer imaging and the study of novel imaging modalities.

The Institute has also promoted the study of imaging agents and probes, especially those that have the potential to better pinpoint the molecular signature of tumors. In structuring these grants, NCI is hoping to fund them so that they have a good shot of making it through the assessment of the technology's clinical utility. The Phased Innovation Award has been the springboard for some of this work. Grant awards in this area were announced last spring.

Another new program at NCI aims to enhance multidisciplinary research and reach out to investigators that have not had access to materials and a research environment available at institutions like the National Institutes of Health. Modeled after the developmental therapeutics program, this new program facilitates better access to chemistries, production resources, scaling of production, and other areas. A new Request for Proposal was released that focuses on the development of clinical imaging agents.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

Research is focused on several phases of the technology development process, including those that expand discovery. A new Request for Proposal is out on ultrasound research interface, as well as an RFA (request for applications) on small animal imaging resource programs.

Looking at breast cancer screening technology development and testing specifically, efforts are underway through Dr. Dahl's office to partner academic institutions with small business and research cooperative groups. Study of digital mammography is a case in point.

Information systems development

There is a tremendous need for information systems development in the area of high throughput biological analysis, according to Dahl. To optimize technology discovery and development, NCI director Richard Klausner, M.D. has played an active role in promoting database creation and management storage that will permit modeling, manipulation, and hypothesis generation.

NCI is actively building a Biomedical Information Science and Technology Implementation (BISTI) plan. In part, through an NIH director forum, recommendations for BISTI's development are emerging. Key recommendations include supporting planning grants in national Centers of Excellence, furthering investigator-initiated research, bolstering the Information Storage, Curation, Analysis and Retrieval (ISCAR) program, coordinating work across NIH, and building a computing infrastructure. Initiatives were slated for announcement in June 2000.

Initially, investments will focus on traditional, low risk, evolutionary projects, but BISTI will move towards long term, higher risk investments.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×
Unconventional Innovations Program

Under the management of Dr. Dahl's Office of Technology and Industrial Relations, NCI is trying a new nontraditional multidisciplinary program through its new Unconventional Innovations Program. Besides reaching out to recruit new investigators and build multidisciplinary teams, the program is actively engaged in translating technology into other nontraditional domains. The program is modeled after the Defense Advanced Research Projects Agency (DARPA) and emphasizes technology maturation and export.

This program solicits contracts for the development of Novel Technologies for Noninvasive Detection, Diagnosis, and Treatment of Cancer. According to the most recent solicitation brochure, the program is “specifically soliciting projects to develop technology systems or systems components that will enable the sensing of defined signatures of different cancerous and precancerous cell types or their associated microenvironment in the body in a way that is highly sensitive and specific, yet non-intrusive. The highest priority is for systems that can either support or provide a seamless interface between sensing/detection and intervention. ”

The first five awards totaling $11.3 million were issued in 1999 and Dahl anticipates investments up to $18 million over three years in 2000. Within the next five years, NCI plans to invest $48 million in this program. Taking a new tack, the Unconventional Innovations Program is putting its major focus “on the development of technology that will target quantum improvements in existing technologies or entirely novel approaches, rather than incremental improvements to state of the art,” states an NCI brochure describing the program.

Integrating detection and care

Through most of these programs, NCI is making a concerted effort to move into a prevention, precancer focus, thus finding disease before masses are palpaple. In addition, the

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

Institute is also working to integrate prevention, detection, diagnosis, and treatment efforts in these programs. The goal is to build a common platform that enables identifying the tumor's molecular signature, interpreting what it means, and enabling early intervention. Such a program must incorporate resources for sensing, communication, data analysis, and judgment into a single platform.

Venture capital investment*

Investment of venture capital is key in providing start-up monies for developing new screening technology, “but investment trends have not been favorable to healthcare,” according to William McPhee, who heads a venture capital fund that exclusively invests in medical imaging.

Venture capital (VC) firms view investment in the healthcare sector as a high-risk proposition. Major hurdles that stand in the way of investing in the screening sector include unfavorable reimbursement and slow adoption rates for new screening technologies. Regulators and others view incremental improvements in screening accuracy and medical imaging skeptically, as adding little value over existing screening techniques.

“It's very difficult to rationalize investment in breast cancer detection technologies,” said McPhee. Typically, venture capital firms raise capital, make investments, build a company, and then harvest - or sell the assets. Until the last two years, a venture capitalist' s investment horizon was between four-to-ten years. From investment, the cycle took about five years, with approximately another three-to-four years to harvest. That cycle has changed radically in the last two years, largely driven by the Internet, with astronomical investments and rates of return. The

*

Based on a presentation by William McPhee, Managing General Partner, Mi3 Venture Capital, a venture capital fund that is focused solely on medical imaging.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

investment-to-harvest cycle is down to 18 months. “Never before has so much venture capital money been deployed so fast for such high returns, but these rapid investments and high returns are not occurring in healthcare, which is no longer the darling of investors,” according to McPhee.

The venture capitalist looks for return on investment (or ROI). The venture capital funds are booming because the ROI is at an all-time high, hitting 143% last year. In the 4th quarter of 1999, venture capital firms pumped $160 million dollars per day into entrepreneurial companies, with many of these returns driven by the Internet. McPhee does not believe that this is a sustainable rate of return, yet even so, he sees screening as a poor contender for making back high returns quickly.

Today, the VC industry increasingly looks to score a home run, focusing on the “super deal,” rather than investing in a broader portfolio of assets. To make this happen, venture capitalists look for an industry-dominant company that plans to go public in two years. In the past, approximately 20% of companies that went public didn't turn a profit, but now, roughly 80% that go public don't turn a profit, although the recent downturn in Internet and technology stocks has put a damper on that trend.

Still, the VC industry looks for a superstar management team with leaders that can bridge the gap between science and the business world. Venture capitalists look for a proprietary product with an immense market, sales projected at $1 billion or more, clearly identified customers, no dominant competitors, and excellent distribution channels. Other factors that venture capitalists look for before they invest today are a digestible first round and ten times their investment back in five years.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

Healthcare simply cannot generate these rates of returns in the current environment. Most importantly, in the last few years, device companies have not proven to make money over the long haul for venture capitalists.

Other factors make health care, particularly screening technologies, a poor contender for investment. Assessing the competitive landscape of technologies in healthcare is tough because of immense competition on the horizon. Another dilemma facing the VC industry is how to move medical culture to change practices and implement new technology. Not only must VC firms contend with how long it will take them to get approval for their technology, but they must also consider— to what extent— an innovative technology can supplant the gold standard, and the medical community's resistance to using new technology. McPhee believes that the broad use of mammography as a screening standard will make it difficult to introduce other technologies, no matter how powerful they are.

Investing in new screening technologies is especially difficult because many novel diagnostic techniques have no immediate therapeutic implications. Reimbursers simply won't pay for the technology if the therapeutic implications are uncertain. McPhee argued further that contemporary low or static reimbursement structures, particularly coming from the Health Care Financing Administration, discourage venture capital investment. Not only does HCFA determine Medicare reimbursement for screening, but HCFA rates also set the pace for managed care, creating strong incentives for inertia in VC investment.

Other considerations that the VC industry must take into account include defining the customer and assessing true value for new technologies. Venture capitalists have little confidence in finding strong management teams in the healthcare sector, and perceive healthcare (and breast disease in particular) as a high-risk, low-reward sector. Distribution is also daunting

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

from the venture capitalists' perspective because it is difficult to assess and gain distribution in a highly consolidated industry. Building your own sales force is virtually impossible. Another major barrier is an underlying cottage industry mentality and resistance to standardization in healthcare.

Not surprisingly, venture capital investment in healthcare has plunged from about 25% traditionally to about 11% in the last quarter of 1999, with about 3 points of that going into Internet-related healthcare ventures. Thus, the real number going into non-Internet related healthcare has dropped approximately 8%.

In evaluating medical imaging, McPhee says that his venture capital firm looks at imaging as an integrated sector, rather than as bits of technology. Looking beyond his firm, he says that medical imaging is misunderstood and undervalued in terms of the size and scope of its implications. He views imaging as “the fulcrum of most decisions in the life sciences,” not unlike genetics.

McPhee's venture capital firm works closely with corporate partners, including Kodak and Bracco. The practice plan of Indiana University's Department of Radiology is also a limited partner. His firm also works with a strategy firm to do the market analysis, including assessing the adoption rate and the prospects for reimbursement.

In evaluating various market volume scenarios, McPhee believes that unless a technology can do both screening and diagnosis, it will prove very difficult to justify the capital risk. The “special breast ” market has been of considerable interest to venture capitalists. This market would include women with dense breasts, scar tissue, and implants. However, it also suffers from similar limitations.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

To alter this picture, it would require reconfiguring reimbursement structures to match true activity-based cost structures. In thinking through cost structures, payers often have a very limited view of technology. However, when new equipment is adopted, it changes work process flow and storage issues that can radically change the cost of a delivered unit of therapy.

Further compounding the difficulties in mammography are traditional, yet artificial separation of the technical and professional aspects, arbitrarily divorcing accountability for the joint technical and professional aspects of any new technology. National Institutes of Health initiatives to integrate reimbursement with technology development are a step in the right direction, but much more work has to be done. NIH budgets are miniscule in contrast with big industry.

McPhee recommended more pooling of the resources of government, healthcare, and industry with venture capital to achieve commercialization of new breast cancer detection and treatment technologies.

As for the potential impact of better coverage for clinical trials, fast tracking PMAs, and other initiatives that might bolster technology development, McPhee said that these might help, but only if they addressed the investment cycle of the venture capitalist.

Evidence Required for Approval by the Food and Drug Administration: FDA Regulation of In Vitro Diagnostic Requirements*

In regulating how devices are reviewed and assessed before the Food and Drug Administration allows them to enter the market, FDA is guided by two federal laws: the Medical Device Amendments of 1976 and the Food and Drug Administration Modernization Act

*

Based on a presentation by Steven Gutman, M.D., M.B.A., Food and Drug Administration, division director, clinical laboratory devices.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

(FDAMA) of 1997, according to Steven Gutman, M.D., director of clinical laboratory devices at FDA.

The Medical Device Amendments of 1976 established general criteria that must be satisfied for pre-market review, including specifying research requirements in place during development of devices and the data and labeling requirements of importance in premarket review. General controls set forth in the Medical Device Amendments of 1976 require that companies register and list their device with the FDA, sign off that they adhere to good manufacturing practices, and report device failures. FDA requires both an independent evaluation of the data brought before it, as well as an independent evaluation of the product's labeling. According to the 1976 amendments, devices in the market by 1976 were grand-fathered in as old devices.

FDA identified two pathways to market for in vitro diagnostics in the 1976 law. A crucial distinction is whether a device is considered a new version of an old device or a totally new device with no predicate. That distinction determines the pathway to market for the device. For new versions of old devices, companies must file a premarket notification or so-called 510(k) submission (named after the 510(k) provision of the law in which this review mechanism is delineated). For devices for which there is no predicate, “companies must demonstrate de novo that its product is safe and effective by filing a premarket approval application or PMA,” said Gutman.

The Premarket Notification 510(k) submission is the predominant way that companies seek market approval for laboratory diagnostics. Approximately nine hundred 510(k) submissions are filed each year. Companies must demonstrate that the new version of the laboratory equipment is “substantially equivalent,” said Gutman, meaning that “it is no worse than products on the market in 1976. However, it is not required to be any better.”

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

By contrast, the Premarket Approval Process (PMA) process is rarely used by sponsors, with submissions accounting for one-to-two dozen each year. The PMA process is administratively more demanding for sponsors.

In conducting research required for FDA approval, companies have a variety of oversight options for studying in vitro diagnostics. If leftover samples are being used without patient identification, studies may be performed with waiver of informed consent and expedited or abbreviated IRB (Institutional Review Board) oversight. If patient identifiers are used but information is not reported back, informed consent is generally required, however, IRB oversight can often again be expedited or abbreviated. If information is actually reported back to patients, use of a test requires an Investigational Device Exemption requiring both informed consent and IRB oversight. For devices that pose significant risks to patients (including the risk of use of information being reported back to the physician or patient), FDA review of these is required before research can be initiated. For devices that do not posse significant risks to patients, oversight is assigned to the local IRB.

Labeling requirements for in vitro diagnostic devices are outlined in Section 809.10(b) of the Code of Federal Regulations which is published yearly. In vitro diagnostic devices must be labeled with FDA proprietary and established names for each device, intended use(s), a summary and explanation of the test, and the general procedures used in conducting the in vitro test. When appropriate, the sponsor must provide information on reagents, instruments, specimen collection and storage. The label must specify how the laboratory test is performed, how the results are calculated, as well as the test's analytic and biologic limitations.

Other requirements included in the 809.10(b) regulations call for specification of the expected range of values in the intended population(s), the product's specific performance

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

characteristics, a bibliography, identification of the name and place of business of the sponsor, and a date of the package insert.

The most important labeling element is the product's intended use(s) which may determine the type of review, the nature of questions asked, and the minimum data sets needed for approval. The most important aspects of the test's performance review are a demonstration of accuracy or bias in test results, precision or repeatability, analytical specificity and sensitivity. If the test is a quantitative test, linearity must be defined. If it is qualitative, cut-offs and equivocal zones must be clearly identified.

New devices are most commonly compared to either predicate devices and/or reference methods to establish performance. For quantitative tests, a linear regression analysis will satisfy FDA criteria for establishing accuracy. However, for qualitative tests, a dichotomous evaluation is typically used.

FDA examines precision or repeatability of a diagnostic test before it is approved. The NCCLS standard (EP5) works well for quantitative tests and allows for an Analysis of Variance Analysis (ANOVA).

Reviewing analytical specificity is a major challenge, according to Gutman. “We always ask for relevant interference studies.” However, premarket studies may not always span the full biological spectrum of expected use and as a result specificity is often observed to change with more widespread test use. Analytical sensitivity criteria are most commonly and practically defined in terms of functional sensitivity—the precision at the lower cut-off level.

To satisfy FDA clinical performance pre-market criteria, sponsors can submit to FDA the history, experience, and/or literature regarding the old test. With a new or not well-established test, clinical performance will be a core review issue.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

In all cases, FDA asks about clinical validity and clinical utility. Clinical validity is evaluated using biological and clinical endpoints, clinical diagnostic sensitivity and specificity, receiver operator curve analysis and predictive value analysis. FDA attempts to identify spectrum bias as well.

FDA struggles with clinical utility, examining the biological performance against set endpoints. However, FDA studies are not focused on clinical outcomes, nor do they address costs or societal issues.

In assessing the scientific methodology, FDA relies on the NCLSC standards, other voluntary standards, previous FDA guidances, and existing literature. In determining whether the product was developed using good science, FDA reviews the up-front protocol, the hypothesis, statistical plan, and data analysis.

In reviewing the science used to test the product, FDA determines whether or not the population sampled approximates the population for whom the product is intended, whether the testing performed matches its intended use, assesses the appropriateness of criteria for study samples, considers whether the performance analysis adheres to standard laboratory practice, evaluates the context of use (e.g. home, central lab, or hospital), and addresses labeling issues.

The scientific hypothesis drives FDA's review. “Sponsors have a wide range of choices to choose from [in selecting the hypothesis] and we encourage sponsors not to cover all bases, ” said Gutman. “Often sponsors start by examining the test's “best intended use.”

In assessing whether a test meets muster, sponsors must frame the test in terms of what they consider disease, whether the test is to be used for screening, for confirmation of disease, to sub-classify and refine post-treatment, monitor treatment effect, predict course, or establish a primary prognosis.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

Gutman described how FDA scrutinizes tumor markers, such as prostate-specific antigen (PSA). If PSA is to be used for screening, FDA labeling “avoids sensitivity and specificity like the plague,” according to Gutman since these parameters cannot reasonably be established using conventional study techniques. If its intended use is for monitoring tumor recurrence, FDA will require objective evidence of tumor behavior, longitudinal study of the given study population over time using both subjective and objective endpoints, and the methodology underpinning risk assessment.

In 1997, the Food and Drug Modernization Act (FDAMA) responded to industry concerns that the FDA process was burdensome. Under FDAMA, there is generally more flexibility, and a more interactive process between FDA and the sponsor, allowing more rapid communications with companies, and generally providing more flexibility for companies developing new diagnostic technologies, according to Gutman. The modernization process continues to evolve and the use of good science makes for better laboratory practice, good business, and good regulation.

The FDA Process: An Industry Perspective*

John Neugebauer, vice president of marketing from TransScan Medical Imaging, presented a snapshot of how industry sponsors—particularly his company—see the FDA pre-market approval process. TransScan was founded in 1992 in Israel. With venture capital funding, it developed electrical impedance technology. The technology was approved as an adjunct to mammography in April 1999.

*

Based on a presentation by John Neugebauer, vice president of marketing, TransScan Medical Inc., Ramsey, NJ.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

Neugebauer described the FDA pre-market approval process in a nutshell as “mandatory, difficult, lengthy, costly, and ongoing.” He described the PMA process for new breast imaging technology as especially cumbersome. Other problems hinder moving emerging detection technologies forward, such as the mammography lobby exerting a major restrictive force on new technology development. FDA can regulate and enforce, but it can't satisfy all constituencies, often putting the FDA in a no-win situation.

After a sponsor obtains FDA approval for a device to go to market, the sponsor often views its relationship with FDA as “necessary, reasonable, fair and equitable, and a barrier to competition.”

The mandatory requirements placed on sponsors of new devices Neugebauer likened to obtaining a Good Housekeeping Seal of Approval. However, that approval does not guarantee success in the market, while failure to gain approval can kill the device, the company, or both.

Nearly all parties involved in the FDA device approval, including industry, regulators, trade associations, and lobbies, concede that the process is enormously difficult, according to Neugebauer. Indeed, former FDA staffers often function as FDA consultants to device manufacturers to help expedite the process. Politics can easily enter into FDA panel's review process, with politics driving a PMA rather than a 510(k). After a pre-market review, it is hard to determine how to proceed to best expedite approval.

Moving a device through the FDA process can last five years or more, as it did for TransScan moving its electrical impedance technology through the process. Performing clinical studies is costly. For example, Neugebauer says that a company may have to pay at least $300 per patient to perform one test, making it imperative that the company is able to raise $20 million.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

“There is almost no way for the company to recover these costs,” he said, because reimbursement is low and post-marketing surveillance adds more costs. Associated costs needed to get a device developed and out to market are high, including costs for management, clinical studies, service and support, consultants, data analysts, and professional services.

Neugebauer estimated that it cost TransScan approximately $7.5 million to bring electrical impedance technology to market. Other breast detection technologies that have yet to gain approval are costing sponsors much more, he estimated, citing Neo vision, Sonic CT, Wavesonics, Mediscience Technology, Imaging Diagnostics, and others.

To improve upon the existing FDA process, Neugebauer suggested several remedies. “Maybe, the classification of the device should be changed...and not all new devices should be class III devices.” He also questioned whether FDA was best positioned to evaluate emerging breast cancer detection technology. Perhaps NCI would be a better alternative, he offered. FDA has limited staffing and funding to allow field visits to see how a device works in practice. Increased FDA support might help remedy the situation. However, Neugebauer said that interagency support might help expedite the process from idea to market.

Other strategies that he recommended included seeking alternative funding, conducting more studies at government hospitals, and moving the device review panel outside FDA.

ACRIN – A New NCI Cooperative Group for Clinical Trials of Medical Imaging *

The American College of Radiology Imaging Network (ACRIN) is the first large-scale collaborative clinical trials group devoted to the developing and conducting clinical trials of medical imaging. Supported by the National Cancer Institute (NCI), ACRIN was launched in

*

Based on a presentation by Bruce J. Hillman, M.D., University of Virginia School of Medicine

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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1999 and funded by NCI at more than $22 million for a five-year period through 2004. According to Bruce J. Hillman, M.D., Network Chair, “there is really no other major trial structure” for rigorous assessment of diagnostic imaging and imaging-guided therapeutic technologies.

An advantage of the new multi-institutional consortium is that it is structured to work with other NCI consortia, industry, and insurers. Unlike other multi-institutional study groups, ACRIN is “more virtually organized,” said Hillman. With participating institutions far away from each other, investigators communicate with each other almost entirely by email and telephone. All of the text data and images are transmitted via the Web and put onto an electronic database. Besides virtual communication, the group holds biannual meetings and encourages industry support.

ACRIN's fundamental objective is to improve the quality and length of lives of cancer patients by evaluating emerging imaging technologies; studying the value of widespread imaging practices; evaluating the impact of imaging on outcomes and costs; extending participation in clinical trials; and training researchers in conducting clinical trials.

ACRIN's infrastructure integrates funding, study methods, data acquisition and management, informatics, regulatory assistance, quality control, financial management, analysis, and research dissemination under one rubric. To get a clinical trial up and running, NCI's Cancer Therapy Evaluation Program (CTEP) must review and approve it.

ACRIN's digital mammography trial, which will be headed by Etta Pisano, M.D., will test digital vs. conventional film-screen mammography for purposes of screening. The trial is still in the developmental phase. Trial investigators hope to study digital mammography in nearly

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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50,000 consecutive asymptomatic women at 22 sites across the United States using digital mammography machines from four manufacturers (Trex, Fischer, Fuji, and General Electric).

The trial will not be a randomized controlled trial. All women will undergo both imaging studies. Images will be read independently by two separate readers, but readers will not be blinded to history. Work-up occurs based on the results of both examinations. As planned, the study will be adequately powered to see whether unnecessary recalls for follow-up tests can be reduced with digital mammography.

The major outcomes measures will be area under the curve for the ROC (receiver operating characteristic) curve, sensitivity, specificity, positive predictive value, and negative predictive value of digital mammography. Secondary goals are to compare the accuracy of softcopy vs. printed film mammography. The digital mammography trial also will be designed to evaluate downstream costs, including both financial and quality of life costs.

Additional areas that trial investigators hope to clarify include the clinical significance and progression of ductal carcinoma in situ (DCIS), an area of considerable controversy. The dense breast population, which cannot be imaged optimally with standard film-screen mammography, will be evaluated separately. Other areas that ACRIN would like to address in the trial concerns both the efficacy of soft-copy vs. hard-copy display and computer aided diagnosis (CAD).

At the time of Hillman's presentation, an administrative review with CTEP was scheduled on July 21, 2000.

Another ACRIN breast cancer trial that has been approved for co-development by the CALGB will evaluate magnetic resonance imaging (MRI) results as a predictor of response to chemotherapy of stage III breast cancer.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Several other cancer imaging trials unrelated to breast cancer are in various stages of development, including trials evaluating CT (computed tomography) vs. MRI vs. FIGO for staging early cervical cancer; assessing PET (positron emission tomography) to quantitatively assess response to chemotherapy for non-small cell lung cancer; determining optimal formatting for CT colonography; spiral CT for lung cancer screening; and embolotherapy plus chemotherapy vs. chemotherapy alone for metastatic colorectal cancer of the liver.

In May 2000, NCI's Executive Committee approved the ACRIN trial concept for digital mammography. The trial must also pass CTEP review. Hillman hopes that ACRIN will be able to address outstanding issues raised in its administrative review, secure IRB approvals, and start recruitment in October 2000.

ACRIN's next public meeting will be held in Washington DC October 14-15 and information about ACRIN activities can be found on its Web site www.ACRIN.org.

Statistical Design for Clinical Trials*

Before securing Food and Drug Administration (FDA) approval, new breast cancer detection imaging devices must first demonstrate accuracy, namely that the new system (i.e. the device and the reader) can differentiate between the presence and absence of disease, according to Alicia Y. Toledano, Sc.D. This requirement must be satisfied before the new technology's merits and limitations are assessed within the context of a screening or diagnostic trial.

Once the device's accuracy is demonstrated and the device becomes widely available, the community using the device can begin to assess its effectiveness. Under a best-case scenario, a mortality reduction may be demonstrated with further clinical trials, according to Toledano.

*

Based on a presentation by Alicia Y. Toledano, Sc.D., Center for Statistical Sciences, Brown University

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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When the General Electric digital mammography machine became approved by the FDA in January 2000, the manufacturer's main goal in filing its PMA) was to demonstrate substantial equivalence to conventional film-screen mammography.

According to public information that Toledano shared from FDA's Radiological Devices Panel approval (also available on www.fda.gov/cdrh/rdp/html), the PMA was approved with conditions, including the requirement that in using digital mammography, soft-copy workstations are used as an adjunct to hard copy, that the labeling's executive summary stress the difference between the study population and a true screening and/or a diagnostic population, and that the approval of the soft-copy technology be expedited. According to the Radiological Devices Panel 's approval statement, panelists agreed that “requiring a post-market study is a waste of time and valuable resources. ”

Toledano described the history of digital mammography manufacturers working with the FDA to secure approval for digital mammography machines. In early 1995, manufacturers made it clear that they were not interested in a large screening trial.

In June 1996, FDA issued a guidance document on how manufacturers should proceed with digital mammography, recommending an agreement study that compared digital with conventional film-screen mammography. Broad intra- and inter-reader variability, even with conventional screen mammography, was a concern raised by the panel, as was divergence between hard and soft-copy mammography readings.

According to Toledano, the guidance document was amended in August 1998, stressing that digital mammography was being watched closely because of its potentially large public health impact. The guidance advised sponsors to aim to make digital mammography at least as sensitive and specific as film-screen mammography. However, FDA reached no closure with the

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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manufacturers at that time. In June 1999, FDA pulled the 1996 guidance. Offering no replacement, the manufacturers began working individually with FDA.

In evaluating a new screening device, statisticians must consider issues, such as high sensitivity (the test's ability to detect everyone with cancer) against low specificity (false positive) results in asymptomatic individuals, according to Toledano.

When a device is intended for use in diagnosis, statisticians must recognize that they are dealing with a symptomatic patient population, aim for a relatively high specificity (so that cancer is ruled out in anyone that doesn't have the disease), and build on the high sensitivity inherent in conventional screening, noted Toledano.

Both false positives and false negatives have adverse consequences. With false positives, patients often undergo unnecessary diagnostic testing, and invasive procedures such as biopsies, and this cascade of events can be upsetting to the patient and costly to the health care system. It can also make patients fearful of repeat breast testing. False negatives also have important downsides, such as missing disease, resulting in later diagnosis, and possibly poorer long-term prognosis and outcomes.

Safety and effectiveness, to some extent, depend on what context the device is going to be used, noted Toledano. How a device's sensitivity and specificity are balanced depend on whether it is used for screening, diagnosis, or both. The consequences of a false negative or false positive must also be balanced.

In the context of evaluating digital mammography against conventional film-screen mammography, Toledano said that “there is a major problem: film-screen mammography does not even agree with itself.”

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Another problem is that radiologists have different thresholds for interpreting a screening mammogram. “Given the same imaging study, one radiologist may urge normal follow-up, another may call for a repeat study in six months, and a third may favor diagnostic work-up, while a fourth may recommend a biopsy,” said Toledano.

Interpretation of the receiver operator curve may also prove daunting with breast cancer, particularly because the disease is binary or the test result has three or more possible values, according to Toledano. Other statistical difficulties pertain to multiple reader studies. In evaluating the accuracy of a device when used by multiple readers, several key questions must be answered, such as how often readers disagree on how they interpret the same case, how large those differences are, and how much reading variation occurs across readers.

Yet measuring the performance of a consensus reading does not match the average performance of the readers in a study, Toledano said, adding that study readers are not equivalent to readers out in the community, she pointed out.

Thus, in designing a clinical trial to measure accuracy, investigators need to estimate the number of readers needed, as well as the number of patients required to prove their case. In assessing a screening test, “the power of the study is maximized when 50% of patients have the disease.”

In conclusion, Toledano pointed out that for clinical studies to prove accuracy of a new technology, the study must present ROC curves, assess sensitivity and specificity, use multiple readers that work independently, and a reference standard.

Agreement studies have important limitations, namely they do not show superiority to existing technology, according to Toledano. Large intra-observer and inter-observer variation in interpretation can also pose a problem.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Choosing appropriate study endpoints*

ECRI is an independent health technology assessment group in Plymouth Meeting PA that evaluates many of the devices that the Food and Drug Administration reviews. Its approach is distinctly different from FDA's review process, according to Charles M. Turkelson, Ph.D. Rather than determining whether a technology is safe and meets the claims on its label, ECRI assumes the societal (or population-based) perspective and considers whether using a specific medical technology is cost effective, a rational investment, and will benefit the health outcomes of the population that the technology is intended for. Aiming to ensure independence, ECRI requires that all staff engaged in technology assessment satisfy very strict conflict-of-interest guidelines.

In evaluating emerging technologies, ECRI often uses decision modeling to model uncertainty. Decision modeling offers a lot of advantages in modeling benefit and the cost effectiveness of emerging technologies. The technique is one of the least used tools for assessing new technologies. An important advantage of decision modeling is that it can link together the impact of a detection technology with the effectiveness of treatment and treatment outcomes. It is a particularly useful technique when there is a dearth of data from clinical trials.

Turkelson made a strong case for looking beyond conventional measures of test accuracy, showing, for example, that high accuracy can either minimize false positives at the expense of false negatives, or work the other way around. Two equally “accurate” tests can have very different health impacts, he pointed out.

Recognizing that accuracy (sensitivity/specificity) “tells you nothing about whether women will benefit,” Turkelson explained that ECRI focuses on increased survival and enhanced quality

*

Based on a presentation by Charles M. Turkelson, Ph.D., chief research analyst, ECRI Health Technology Assessment Information Service.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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of life as the key endpoints in its technology assessments. When screening tests have no effective treatments to go with them, analysts consider the impact of the test on women's quality of life. This consideration is factored into ECRI's decision modeling analyses. Another factor that ECRI incorporates into decision modeling would be the merits of adding a new screening test versus screening more women or providing better therapies.

Several biases are accounted for when ECRI evaluates detection technologies. As Turkelson explained, device manufacturers are often in a bind with the FDA when they test new detection technologies because they are often limited to testing the modality in a discrete population of women. An unintended effect of limiting the study population is that the technology's effectiveness could be overstated or understated, depending on which population the technology is tested in and to whom it is being applied.

Spectrum bias is introduced when there are key differences between a study population and the clinically relevant population. One form of spectrum bias occurs when the technology is tested in the sickest of the sick. When the study population is limited to that group, the true positive rates may be inflated. When tested in a more heterogeneous population, the test may not perform as well.

Spectrum bias can also occur when the test is evaluated in the wellest of the well. Although studies that test technologies this way do it to ensure that the test is not positive in everyone, evaluating the technology in a very healthy subset can skew performance testing. Far more healthy patients might be free of other diseases that cause false positives. Test referral bias can also yield misleading assessments of a new technology. If in testing the technology, it is not tested on patients with negative results with the gold standard test, the test's value in that subset can be hard to discern.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Another important bias that can confound a technology assessment is reader bias. Unless those performing or reading the test are blinded to the patient's history, a reader might read the results using the information from the history, thus leading to downgrading or upgrading a result. Unblinded studies can make a technology look much better than it is. Ideally, in assessing new technologies, it is best to test them in a population similar to that of interest, blinding investigators to patient histories, and factoring in related factors that could influence the technology's benefit, utility, and cost.

Coverage Issues from the Innovator's Perspective*

Device manufacturers often find it daunting to figure out what criteria and standards of evidence they must satisfy to pass muster for Medicare coverage, according to Susan Bartlett Foote, J.D., describing a coverage decision-making process at the Health Care Financing Administration (HCFA) that has been “in flux for years.” Foote continued: “As devices emerge, it is critically important to understand the evolving nature of HCFA law and policy.” She maintained that this evolving policy has contributed to an uncertain atmosphere for device developers because they don't know what standards HCFA will hold them to. At the same time, Foote pointed out that although the new Medicare Coverage Advisory Committee and HCFA are considering several mechanisms for coverage decision-making, so far, “they have not clearly articulated and completely specified” precise review criteria.

*

Based on a presentation by Susan B. Foote, J.D., University of Minnesota

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Foote expressed concern about HCFA's use of the drug model as the dominant model for evaluation of new devices. It is a model that “does not mesh well with the complexities of the device industry,” she pointed out, articulating several reasons why developing new devices can be significantly different than developing new drugs. Manufacturing of a new device involves engineering technology and is often done incrementally because it involves developing new hardware, software, and tools to make it work. The devices themselves may cost thousands of dollars each, making distribution of devices for clinical trials very expensive. Since most device companies are very small, the upfront costs of innovation are high. In contrast, most pharmaceutical firms are large multi-national enterprises. While drug development is expensive, once the product is discovered, the cost of producing the tablets small relative to highly engineered devices, according to Foote.

Under current law, HCFA may cover investigational devices (that is, not yet approved by FDA) but only those that are not breakthrough products. It is unclear, but unlikely, that the new policies for reimbursing clinical trials, which have not yet been implemented, will apply to all investigational devices.

Device innovators also have far fewer resources at their disposal than with pharmaceutical developers because they are often small start-ups with fewer than fifty employees, according to Foote. The device manufacturers “simply don't have the resources to match what drug companies can provide in terms of data and evidence,” Foote cautioned.

In comparison with the drug development field, which has built a large outcomes research and cost-effectiveness base, device manufacturers do not have the same capacity and there “has been no similar investment in evaluating the economics of new devices,” she said.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Foote pointed out that there is not yet a field that can best assess the economics associated with new device development. The pharmacoeconomics model does not fit, she maintained. As Medicare policy continues to evolve, Foote urged regulators to “know your innovators” and not assume that devices fit the drug model. Offering a snapshot of recent developments in coverage criteria, Foote pointed out that efforts to promulgate a clear rule on coverage criteria failed in 1989 and again in 1996.

In April 1999, the Health Care Financing Administration announced three-part reform and its intent to develop a new Medicare coverage decision-making process. The Medicare Coverage Advisory Committee was established to make recommendations on how to evaluate new technology for Medicare.

May 16, 2000, HCFA issued a notice of intent stating that lots of new technology is open to being defined. Under consideration are the following criteria: determining whether “the new technology is ‘medically beneficial',” a concept that Foote says has an “uncertain interpretation.” If a technology satisfies criteria for medical effectiveness, HCFA may examine whether there is either a medically beneficial or less costly program alternative. If the new technology has equal medical benefit, HCFA may cover the new technology, but only if total costs to the Medicare program are lower.

The criteria are now being debated. The original 30-day comment period closed in July, but no proposed rule has issued. HCFA has scheduled a town meeting to discuss the proposal in September, 2000. When new criteria are announced, Foote hopes that the unique complexities of the device industry will be taken into account. Lacking definitive criteria, device manufacturers face an uphill battle in knowing what to shoot for in satisfying HCFA requirements, she concluded.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Medicare Coverage Advisory Committee*

The mission of the Medicare Coverage Advisory Committee (MCAC), established in 1999, is to evaluate the evidence on the effectiveness of services that the Health Care Financing Administration (HCFA) is considering for coverage under Medicare, according to Harold C. Sox, Jr. M.D., chair of the Committee's Executive Committee.

In reviewing a specific item or service, MCAC first considers the validity of the evidence of an effect on health outcomes. It then considers the applicability of the evidence to Medicare patients. Finally, it rates the magnitude of benefit in one of six categories: “breakthrough; more effective than the current standard of care; as effective, but with advantages; as effective, but with no advantages; less effective but with advantages; less effective, but with no advantages; or not effective,” said Sox. The magnitude of the health effect is determined from reviewing well-designed studies demonstrating how the new intervention compares with the established intervention.

MCAC is organized into six panels, each of which is composed of 15 voting members, a chair, one consumer representative, and one industry representative. The six panels cover six broad areas: drugs, biologics, and therapeutics; laboratory and diagnostic services; medical and surgical procedures; diagnostic imaging; medical devices and prosthetics; and durable medical equipment.

MCAC also has an executive committee that develops criteria for assessment of effectiveness, develops panel procedures, coordinates panels, develops an annual slate of technology assessments, and approves the submitted panel recommendations to HCFA. MCAC's executive committee is made up of the chair and vice-chair of each panel, as well as one consumer and one industry representative.

*

Based on a presentation by Harold C. Sox, Jr., M.D., Dartmouth Hitchcock Medical Center

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Sox described how MCAC panels conduct technology assessments. The goal of the review process is to be explicit and accountable, which contrasts with Medicare technology reviews that pre-dated the creation of MCAC, which were perceived as closed-door sessions, according to Sox. The panels use an evidence report, which provides a critical evaluation of the evidence. Before generating the evidence report, panel members help frame the questions that the panel, and therefore the evidence report, must answer, he pointed out. Several members help participate in developing the evidence report, while other members of the committee serve as outside experts to review provide an objective view of the evidence report's completeness and objectivity.

MCAC examines validity and general applicability to the population of interest. The highest level of evidence comes from studies that randomize subjects to the intervention and control groups. Well-conducted randomized trials, “eliminate selection bias, isolate the effects of the intervention itself, and help show whether any observed differences in health outcomes are due to the intervention itself,” said Sox. When the panel must rely on observational studies to determine the effectiveness of an intervention, it must take into account potential biases, such as selection biases, that occur when assembling the study cohort, according to the panel's interim operating guidelines. The panels incur a larger burden of proof in making recommendations that are based on observational studies, in which many factors, not just the intervention itself, could influence differences in health outcomes experienced by the intervention group and the control group.

The panel must evaluate external validity based upon the data in the evidence report. Specifically, it must decide whether or not the data applies to Medicare patients and whether the results apply to the usual practice setting.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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In considering emerging breast cancer detection technologies for older women, “better screening may not be the mostly likely way to reduce breast cancer mortality, when you already see a one-third decline in mortality with mammography screening,” Sox said. From a population and cost perspective, he pointed out, innovative breast cancer detection technology may not prove to have advantages over current screening techniques for the Medicare population. Reducing the risk of developing breast cancer may be a more effective method for achieving gains over what is already possible with early detection.

National Cancer Institute's Breast Cancer Surveillance Consortium*

In the early 1990s, the National Cancer Institute examined the feasibility of organizing a Breast Cancer Surveillance Consortium (BCSC) because of compelling evidence that mammography was efficacious and effective in reducing breast cancer deaths from several randomized trials, according to Rachel Ballard-Barbash, M.D., M.P.H. The overriding goal of BCSC is to examine the performance of screening mammography in community practice. Without high quality performance, the benefit of screening mammography predicted from controlled clinical trials will not be realized.

“With a mandate from the 1992 Mammography Quality Standards Act to create such [surveillance] systems, the NCI established the Breast Cancer Surveillance Consortium in 1994 to evaluate population-based screening mammography in the United States,” states a summary of the program on the BCSC Web page <www-dccps.ims.nci.nih.gov/ARP/monitor.html>, referenced by Ballard-Barbash.

*

Based on a presentation by Rachel Ballard-Barbash, M.D., M.P.H., National Cancer Institute, Program Director.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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The BCSC has three major research objectives: (1) to evaluate the performance of screening mammography in the community setting; (2) to assess its accuracy, cost, and quality; and (3) to relate these items to changes in breast cancer outcomes, particularly mortality, late-stage disease, and survival.

The Consortium encourages collaborative research across eight centers across the nation to examine regional, health system, and small population subgroup differences in screening, diagnosis, and follow-up, she said. As envisaged, BCSC is also intended to serve as the “foundation for clinical and basic science research, including the association of biologic tumor characteristics to mammographic detection,” said Ballard-Barbash. The Consortium also supports special research projects.

There are eight BCSC sites around the country and a statistical coordinating center. The Consortium links data from population-based registries, including mammography screening data and pathology outcomes data taken from SEER data (Surveillance, Epidemiology, and End Results program of the NCI). The project uses standardized definitions, data collection techniques, and has in place strict confidentiality protocols, according to Ballard-Barbash.

Because the Consortium collects data within the context of routine clinical practice it's data system allows individual centers to use different data structures for data collection. However, the data definitions are standardized. “Data are translated into a common structure and then sent to the Statistical Coordinating Center without patient identifiers,” said Ballard-Barbash. Then, the Statistical Coordinating Center carries out pooled data analyses.

According to data from 1995-1997, the majority of women in the database are between age 40-49 or 50-59, with 358,183 women (or 30%) in the 40–49 year-old group, and 323,473 women (27%) in the 50-59 year age group. Women under age 40 accounted for a minority of

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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women (n=84,260) or 7% of those in the database. Women aged 60-69 accounted for 224,765 or 19% and women age 70 or more comprised 193,9476 women (16%) of the database.

Examining the data by racial/ethnic group shows that white (not Hispanic) women accounted for approximately two-thirds of the 1995-1997 BCSC population. Black women represented 4% of the population, with most of those women coming from the North Carolina and Louisiana sites. Hispanic women accounted for 7%. Hispanic women were concentrated in New Mexico and Colorado. Asian and Pacific Islanders, Native Americans, and each accounted for 2% of the BCSC population. The remaining 18% were categorized as “Other/unknown.”

The number of screening mammography examinations rose steadily between 1995 and 1997. This occurred because the research centers were building their databases rapidly during this period, often adding more screening facilities and hence obtaining more screening mammography examinations-over this period.

Ongoing research is addressing issues, such as “the effect of variation in definitions on performance issues, sensitivity of screening mammography, evaluating whether or not women are symptomatic or not when they are tested, whether they have ductal carcinoma in situ or not, the performance of screening mammography among women with a family history of breast cancer, the utility of a six-month follow-up examination, and recall rates.”

Investigators are examining the use of the American College of Radiology Lexicon for screening mammography and diagnostic mammography. Other active areas of research include examining performance variation by geography, facility characteristics, and population characteristics.

Consortium accomplishments to date include “establishing a core data set and formatted questions, completing a broad range of projects and papers by investigators at all sites, pooling

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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data to examine the effect on cancer outcomes across all sites, and refunding a number of research centers for the next five years,” according to Ballard-Barbash. The renewal addressed a number of priorities, including increasing the capacity for research on the long-term outcomes of screening, and increasing the representation of under-represented minorities.

Several special research projects are also underway, including ones addressing “novel methods for non-core data collection on risk factors, biological markers, and clinical factors, tracking the diffusion of new technologies, examining quality measures, assessing biologic differences in screen-detected vs. interval cancers, development of statistical modeling, surveying psychological and social consequences of screening, and evaluating screen detection of DCIS.

The Consortium may serve as a data resource for tracking outcomes for women enrolled in the National Cancer Institute's American College of Radiology Imaging Network (ACRIN) trial of digital mammography Meetings have begun with the Food and Drug Administration to plan the development of a system for the postmarket surveillance of digital mammography. These standardized data variables for the examination of digital mammography may include measures of cost to allow evaluation of cost effectiveness, noted Ballard-Barbash.

Additionally, because the Consortium has direct linkages with pathology laboratories, it will be able to track tumor markers, should they become used in the clinical practice of breast cancer screening, she pointed out. Finally, the Consortium is working with the International Breast Cancer Screening Network. Further information on the Consortium can be found on the Breast Cancer Surveillance Consortium's Web page at: <www-dccps.ims.nci.nih.gov/ARP/monitor.html>.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Using Risk Stratification to Tailor Screening Programs*

Risk stratification is critical in selecting the best breast cancer screening technology for women because “not all breasts look alike, there is wide variation in breast density that influences susceptibility to breast cancer, and the ease with which it is detected” with conventional screening techniques, according to Norman Boyd, M.D.

Increased breast density is a well-recognized risk factor for breast cancer, noted Boyd. Density is highest at menarche and declines with pregnancy, menopause and increasing age. Cancer within dense breast tissue is also typically difficult to visualize with conventional film-screen mammography, making it important to determine the best screening protocols for the dense-breast population.

“We don't know yet what the optimum screening strategy is for this high risk population,” said Boyd. It is possible that more frequent mammograms, or using MRI and ultrasound as adjuncts to mammography, or alternative screening techniques might increase the breast cancer detection rate. However, the optimum screening protocols must be studied in a large screening population.

And even though it is well recognized that density declines with advancing age, particularly with menopause, Boyd made the case for further studies of density-for-age risk assessment. He recommended using existing data sets, such as the National Cancer Institute' s Breast Cancer Surveillance Consortium data, to grapple with the problem of increased breast density in escalating risk and interfering with conventional mammography examination. Risk stratification and optimal screening strategies could be determined using the tools of statistical modeling to determine the rate of new tumor formation, its growth, and the rate of detection with various screening protocols, he suggested.

*

Based on a presentation by Norman Boyd, M.D, Princess Margaret Hospital, Toronto, Canada

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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“Capturing breast volume is another method that is currently missing in breast cancer screening,” said Boyd. Correlating volume with density and its impact on relative risk also needs to be further disentangled, he said. Research being carried out by Boyd and Martin Yaffe, Ph.D. of Toronto, is attempting to get at this question.

The reader can be a major influence on interpretation of imaging studies. To reduce reader variability, Boyd suggested using computer aided detection, standardizing density classification, ratcheting up reader training, and using ongoing reader performance testing.

Identifying the Customers of New Technologies and Disseminating New Research*

As new technologies emerge, policy-makers must be cognizant of how the fruits of technological research can best be disseminated to meet national health goals and local health objectives, said Jon Kerner, Ph.D., Assistant Deputy Director for Research and Dissemination, in the Division of Cancer Control and Populations Sciences, at the National Cancer Institute.

Kerner outlined the central goals of Healthy People 2010 in relation to the questions framed by the President's Cancer Panel earlier this year. As new technologies become available for routine practice, policy-makers should keep in mind that resources will need to be spent to close the gap between discovery and delivery if these ambitious health goals are to be achieved, suggested Kerner.

According to a U.S. Department of Health and Human Services January 2000 document, the central goals of Healthy People 2010 are:

  1. to increase the quality and years of healthy life; and

  2. to eliminate health disparities,”

*

Based on a presentation by Jon Kerner, Ph.D., Assistant Deputy Director for Research Dissemination and Diffusion, National Cancer Institute.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

In March 2000, the President's Cancer Panel framed seven questions aimed at helping translate research into practice, particularly aimed at eliminating disparities in cancer care. Those questions are as follows:

  1. Who is under-served for cancer prevention, cancer control, and cancer care?

  2. What must we better understand to address the critical issues and to implement solutions at the macro and micro levels?

  3. What are the social/economic forces that need to be influenced at the national, regional and local levels in order to make a significant difference in the quality and consistency of cancer care?

  4. How is institutional/organizational bias on the part of the researcher overcome developing the questions to pose?

  5. What must be done to ensure that the fruits of research are incorporated into routine practice?

  6. Information dissemination is not enough. How is information consumption stimulated and what do you need to know about your consumers to respond to their needs?

  7. What infrastructure, legislative, policy, and organizational/system changes are necessary to implement solutions?

Looking at the dissemination and diffusion of diagnostic imaging technologies as a good example of the challenges faced, Kerner described how different types of diagnostic imaging techniques range across a continuum of purposes. For example, some imaging techniques have uses that are “specifically procedure-related, such as laparoscopic surgery,” whereas mammography is used for disease-specific screening purposes, he pointed out. Kerner noted that

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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ultrasound is a general diagnostic method that can be used in specific areas. Finally, some imaging technologies are used as a “general technique with multiple applications,” according to Kerner, noting that computed tomography and magnetic resonance imaging fit this use.

In assessing new diagnostic imaging, Kerner said that it involves “technical evaluation, assessment of diagnostic accuracy, diagnostic impact, therapeutic impact, and health impact.”

The American College of Radiology Imaging Network (ACRIN) clinical trial, which will test digital mammography vs. conventional film-screen mammography, is “now under final implementation review at the National Cancer Institute,” said Kerner. In planning the design for the trial, digital mammography will be tested on a total of 49,500 women, including 15% who will be age 65 and over. At present, accrual for the trial is expected to take 1.5 years, with another 1.5 years of follow-up.

Four digital mammography machines made by four different manufacturers (Fischer, Fuji, GE, and Trex) will be studied in the trial. The population will be divided into four groups, with 12,375 women examined on one of the digital mammography machines and will also receive conventional film-screen mammography. The National Cancer Institute, Health Care Financing Administration, and Food and Drug Administration are ironing out specifics pertaining to study design.

In evaluating digital mammography's potential, policy-makers will have to consider several factors, such as “clinical need, technical performance, clinical performance, economic factors, and patient and societal perspectives,” said Kerner. On the clinical end, it will be important to determine whether digital mammography “reduces late-stage incidence and mortality rates for breast cancer, improves positive predictive value, and reduces the number of unnecessary biopsies”. The technical evaluation will require evaluation of “x-ray production and

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

absorption, recording of transmitted x-rays, image development and display,” said Kerner. Economic factors that must be considered include “capital and site costs, operating costs in large vs. small-volume facilities, and follow-up costs,” he said. From the patient and societal perspective, patient acceptance and access to digital technologies should be taken into account.

Kerner highlighted some of the potential advantages of digital mammography, such as “near real-time operation with increased image acquisition and speed, enhanced detection efficiency, enhanced image presentation due to post-processing options, separation of detection, display and storage processes with optimization at each step, optimum application of computer-aided detection methods, electronic archival and retrieval of images, automated incorporation of images into electronic medical records, and compatibility with telemammography requirements (improved access to high quality mammography).” As clinical trials of this new technology move forward, technical improvements will need to be weighed against costs and access issues.

If new imaging technologies like digital mammography prove to be both effective and cost-effective, equal access will then become the issue. If access to digital mammography is limited to resource-rich health care settings, then many under-served populations may be denied access, and health disparities may actually increase. Whether research discovery becomes translated into program delivery through changes in health policy depends, to some extent, on the relationships between researchers and policy-makers, according to Kerner.

He described the importance of investing in new partnerships in cancer control between regulatory sectors of government (e.g. FDA, EPA), research (NIH, NSF), research and application (AHRQ), application and research (CDC), and application sectors (HCFA, HRSA) both in and outside of government. If such partnership investments are made today, then the dissemination and diffusion of new cancer prevention, screening, diagnostic and treatment

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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technologies in the years ahead will be enhanced, and more equal access to new technologies should contribute to reducing health disparities in the future, Kerner concluded.

Access to Screening Mammography*

Utilization of mammography is not evenly spread across the nation 's population, according to Diane M. Makuc, Dr. P.H., Director of the Division of Health and Utilization Analysis at the National Center for Health Statistics (NCHS). Makuc presented a snapshot of recent trends, including the most recent (through 1998) data on mammography use by family income, race, and age.

The information was culled from the National Health Interview Survey (NHIS), an annual nationwide survey of 45,000 households conducted by the National Center for Health Statistics. Mammography utilization data were tracked over six years: 1987, 1990, 1991, 1993, 1994, and 1998. “The dependent variable was whether or not a woman reported having a mammogram within the past two years,” Makuc said. She also presented background epidemiological data on breast cancer incidence and outcomes and she highlighted initiatives that target reaching populations not yet adequately screened and followed for breast cancer.

There are important differences in breast cancer incidence and mortality by race, according to Makuc. In 1996, the incidence of breast cancer in white women was 13% higher than for black women. However, black women had lower survival rates (71% vs. 86%) and almost 40% greater breast cancer mortality (25.3 vs. 18.3 deaths per 100,000 in 1998,

*

Based on a presentation by Diane M. Makuc, Dr.P.H., National Center for Health Statistics, Centers for Disease Control and Prevention. Some of these results appear in Makuc, D.M., N. Breen, and V. Freid. 1999. “Low income, race and the use of mammography”. Health Services Research 34:1 (April 1999, Part II): 229-39.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

age-adjusted). NCHS mortality data reveal a breast cancer mortality reduction among white women since 1989, but death rates have remained relatively stable during the same period for black women. Breast cancer mortality for Hispanic, American Indian, and Asian women was one-third to one-half lower than for white women in 1998 (12.1, 10.3, and 9.8 deaths per 100,000 age-adjusted, respectively).

Having said that, Makuc limited her presentation to white and black women's use of mammography because these groups have “the highest death rates for breast cancer and the most stable estimates of mammography use” over time, she pointed out.

“Substantial outreach efforts have been directed towards increasing mammography use and as a result, recent mammography use (within the past two years) has risen sharply since 1987, with 69% of women age 50 and older reporting that they had a mammogram within the past two years in 1998, compared with 27% in 1987,” said Makuc. A variety of interventions have been used to promote use of mammography. These include media campaigns, system and physician reminders, letters to patients, access-enhancing mobile mammography vans, reimbursement for mammography by Medicare, and outreach by community peer leaders, all of which stress the importance of screening mammography in reducing mortality through early detection and treatment of breast cancer.

According to previous research, mammography use is positively correlated with a higher income and education, having health insurance, urban residence, and having a usual source of care. Older women, especially those age 75 and over, are less likely to have mammography. Previous studies differ concerning whether black women are less likely than white women to use mammography.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

In discussing trends between 1987-1998, Makuc reported on age, race, and income as independent variables. For 1993-1994, education, health insurance coverage, place of usual care, region, and metropolitan status were additional independent variables. Women in the 50-64 age group were analyzed separately from women age 65 and over. The NHIS analysis also examined two distinct income groups: women with family income below twice the poverty level and those with income at least twice the poverty level or higher.

Between 1987 and 1991, mammography use rose rapidly among women 50-64 years of age in low- and higher-income groups, but these increases slowed between 1991 and 1994. Between 1994 and 1998, increases in mammography proceeded more rapidly for lower income women than higher income women. “Nevertheless, in 1998, use of recent mammography was about 35 percent greater for higher income- than low income-women, ” said Makuc.

In the 50-64-year age group, almost one-fifth of white women had incomes that were below twice the poverty level, while 45 percent of black women were in the lowest income group in 1998. Among low-income women mammography use approximately doubled for both white and black women between 1987 and 1991. Black women increased their use of mammography by more than a third between 1991 and 1994, but similar strides were not achieved during this timeframe for low-income white women.

In the next four-year period, between 1994 and 1998, the trends reversed, with low-income white women achieving increased utilization, while rates for low income black women held constant. By 1998, the percent of low-income middle-aged women reporting recent mammography was similar for white women and black women (61% and 57%).

In the 65+ age group, recent mammography use “increased rapidly between 1987 and 1991 and then rose at a less rapid rate between 1991 and 1998 for both higher income and low

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

income women,” said Makuc. Higher income older women had a 27 percent greater rate of self-reported recent mammography in 1998 than low-income women. The gap in mammography use between higher income and lower income older women narrowed from a 67% gap in 1987.

Seventy percent of older black women and about 40% of older white women had income below twice the poverty level in 1998. NHIS data reveal that in 1987, less than 20% of both older low-income white and black women reported having a recent mammogram examination. However, that percentage approximately doubled among low-income white women by 1991 and tripled for low-income black women by 1991. Between 1991 and 1994, older low-income black women's reported use of mammography expanded at a faster pace than it did for low-income white women. Since 1994, self-report of recent mammography use has increased for low-income white women, while the rates for black women remained stable. By 1998, “there were no significant differences between the two groups,” said Makuc.

The remainder of the presentation focussed on exploring reasons why low income black women had higher rates of mammography use than low income white women during 1993 and 1994. Among low-income women 50-64 years of age, NHIS shows that in 1993-94, black women were nearly 30% more likely to report recent mammography than white women (58% vs. 45%) were. By 1998, mammography utilization no longer differed between low-income white and black women.

The NHIS analysis examined the potential contribution of factors that might account for different rates of mammography among low income black women and low income white women, such as insurance coverage, residence, and access to usual care. Makuc said that there was no statistically significant difference in the percent uninsured between black and white women during 1993-94. However, low income black women were twice as likely to have

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

Medicaid coverage (33% vs. 15%), while white women were far more likely to have private health coverage (61% vs. 36%). The percentage of low income women without a usual source of care was the same for black and white women (13-14%), but black women reported using a public clinic or hospital outpatient clinic four times as often as did whites (20% vs. 5%). Place of residence also varied with race. Low income black women were nearly three times as likely as low income white women to live in the central city of a metropolitan area (58% vs. 21%) and black women were also more likely to live in the South than white women (54% vs. 40%).

Using a logistic regression model, Makuc's group was able to show that “insurance coverage, place of usual source of care, and place of residence did not account for the higher screening levels reported by low-income black women compared with low-income white women in 1993-94,” she said. The analysis also shows that “the odds of having recent mammography for low-income women who have private health insurance or public health insurance was greater than 2 compared with uninsured women, ” she said. “Odds ratios for low-income women with either a doctor's office visit or clinic as a usual source of care are greater than 3 compared with women who have no usual source of care. Finally, low-income women who reside in a central city have an odds ratio of 1.5 compared with those who reside elsewhere.”

Makuc discussed some key factors that have bolstered mammography use among low income and black women since 1991, crediting the National Breast and Cervical Cancer Early Detection Program of the CDC (Centers for Disease Control and Prevention) as “by far, the largest single effort to increase screening” in these groups. This program provides grants to State Health Departments in 35 states and 9 American Indian tribes to screen low-income, uninsured, and underinsured women. “The program targets minority women and older women, providing 284,503 mammograms between 1991 and 1995.”

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

State and community-based clinics also provide mammograms to low-income women and community grassroots outreach programs encourage women to get screened.

Yet despite outreach efforts targeting low-income, uninsured, and minority women, access remains a problem for low-income women, who continue to be less likely to report having a recent mammogram than higher income women. In some areas, disparities in screening have been reduced, suggesting that stepped-up efforts to reach these groups have contributed to higher screening levels.

Nonetheless, “black women continue to have higher breast cancer death rates than white women,” said Makuc. One possible explanation is that decreases in breast cancer death rates lag behind increases in screening, she suggested. Another concern is that screening does not necessarily ensure follow-up and treatment needed to prevent breast cancer-related deaths.

The NCI and NCHS have developed expanded questions on mammography that are being asked in the 2000 NHIS as part of a cancer module. These questions will help in understanding the continuing disparities in screening. In addition to asking about time since the most recent mammogram, the 2000 NHIS mammography questions include information on follow-up and treatment of identified cases, she said. Additionally, the survey will ask about age at first mammogram and total mammograms taken to determine whether women are getting regular mammograms.

The context for the mammogram will also be examined more thoroughly, with attention to the type of place where the mammogram was received, the payment source of the last mammogram, whether the mammogram was provided as part of a special low-cost program, the main reason for the mammogram, the main reason for never having a mammogram, or not having one within the past two years, and whether or not a physician advised having a

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
×

mammogram. Women will also be asked if they ever had an abnormal mammogram; if so, what follow-up tests or surgery were done, and the results of those tests.

To collect more reliable information about the Hispanic population, beginning in 1995, the NHIS design over-sampled Hispanic persons. Upcoming analysis of NHIS data will include information about mammography use among Hispanic women.

By incorporating new variables into the most recent survey and over-sampling understudied groups, NHIS researchers hope to have a more complete understanding of breast cancer screening and follow-up among low-income and minority women, concluded Makuc.

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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WORKSHOP SPEAKERS

Bruce J. Hillman, MD

Professor & Chairman,

Department of Medicine-Radiology

University of Virginia

School of Medicine

Susan B Foote, J.D.

Associate Professor & Division Head

University of Minnesota

Harold C. Sox Jr., M.D.

Chairman, Dartmouth Hitchcock Medical Center

Lebanon, NH

Rachel Ballard-Barbash, M.D.

Associate Director

Applied Research Program

National Cancer Institute

Alicia Toledano, Sc.D.,

Assistant Professor

Center for Stat Sciences

Brown University

Lee Newcomer, M.D.

EVP and Chief Medical Officer

Vivius, Inc.

Norman Boyd, M.D.

Princess Margaret Hospital

Charles Turkelson, Ph.D.

Chief Research Analyst

Health Technology Assessment Group

ECRI

John Neugebauer

Vice President of Marketing

Transcan Medical

Bill McPhee

Mi3 Venture Capitol

Carol Dahl, Ph.D.

Director, Office of Technologies and Industrial Relations

National Institutes of Health

Diane Makuc, Ph.D.

Director, Division of Health and Utilization Analysis

National Center for Health Statistics

Jon Kerner, Ph.D.

Assistant Deputy Director for Research

Dissemination and Diffusion

National Cancer Institute

Steven Gutman, M.D., MBA

Division Director

Food and Drug Administration

Clinical Laboratory Devices

Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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Suggested Citation:"Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2." Institute of Medicine and National Research Council. 2000. Developing Technologies for Early Detection of Breast Cancer: Summary of Public Workshop #2. Washington, DC: The National Academies Press. doi: 10.17226/10011.
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