Developing Technologies for Early Detection of Breast Cancer Summary of Public Workshop #2 (2000) / Chapter Skim
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Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2
Developing Technologies for Early Detection of Breast Cancer: Public Workshop Summary #2
Pages 5-53
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From page 5... ...
A second workshop, held June ~ 9-20, 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 1 ~ studied for the early detection of breast cancer, but many barriers must be overcome during the process of development, assessment, and dissemination.
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From page 6... ...
In addition, NCT established a new Of lice 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.
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From page 7... ...
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.
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From page 8... ...
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.
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From page 9... ...
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.
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From page 10... ...
Dahl's office to partner academic institutions with small business and research cooperative groups. Study of digital mammography is a case in point.
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From page 11... ...
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 oftechnology 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.
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From page 12... ...
"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.
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From page 13... ...
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.
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From page 14... ...
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.
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From page 15... ...
Thus, the real number going into non-Tnternet related healthcare has dropped approximately 8°/0. In evaluating medical imaging, McPhee says that his venture capital firm looks at imaging as an integrated sector, rather than as bits of technology.
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From page 16... ...
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.
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From page 17... ...
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.
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From page 18... ...
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)
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From page 19... ...
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.
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From page 20... ...
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.
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From page 21... ...
With venture capital funding, it developed electrical impedance technology. The technology was approved as an adjunct to mammography in Apn]
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From page 22... ...
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.
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From page 23... ...
The American College of Radiology Unaging Network (ACRIN) is the first large-scale collaborative clinical trials group devoted to the developing and conducting clinical trials of medical imaging.
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From page 24... ...
The trial is still in the developmental phase. Trial investigators hope to study digital mammography in nearly 24
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From page 25... ...
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)
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From page 26... ...
In May 2000, NCI's Executive Committee approved the ACRIN trial concept for digital mammography. The trial must also pass CTEP review.
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From page 27... ...
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.
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From page 28... ...
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." 28
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From page 29... ...
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°/O 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.
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From page 30... ...
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.
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From page 31... ...
Several biases are accounted for when ECR} 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.
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From page 32... ...
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.
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From page 33... ...
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.
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From page 34... ...
In April ~ 999, 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.
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From page 35... ...
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.
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From page 36... ...
The s from studies that randomize subjects to the intervention and ~ randomized trials, "eliminate selection bias, isolate the effects .elp show whether any observed differences in health outcomes are said Sox. When the pane} must rely on observational studies to an intervention, it must take into account potential biases, such as en assembling the study cohort, according to the panel's interim =Is incur a larger burden of proof in making recommendations that lies, in which many factors, not just the intervention itself, could outcomes experienced by the intervention group and the control sternal validity based upon the data in the evidence report.
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From page 37... ...
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.
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From page 38... ...
The Consortium also supports special research projects. There are eight BCSC sites around the country and a statistical coordinating center.
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From page 39... ...
Black women represented 4°/O of the population, with most of those women coming from the North Carolina and Louisiana sites. Hispanic women accounted for 7%.
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From page 40... ...
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.
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From page 41... ...
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 Instituters Breast Cancer Surveillance Consortium data, to grapple with the problem of increased breast density in escalating risk and interfering with conventional mammography examination.
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From page 42... ...
Identifying the Customers of New Technologies anti 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 Pane!
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From page 43... ...
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.
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From page 44... ...
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.
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From page 45... ...
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 computeraided 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.
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From page 46... ...
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°/0 higher than for black women.
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From page 47... ...
. 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.
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From page 48... ...
In the next four-year period, between ~ 994 and ~ 998, 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°/O)
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From page 49... ...
By 199S, 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.
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From page 50... ...
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.
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From page 51... ...
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.
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From page 52... ...
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.
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From page 53... ...
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
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