Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers.

BACKGROUND: Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography. Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. METHODS: Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA. Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram. One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. RESULTS: Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3). CONCLUSION: Mammographic breast density appears to be a major risk factor for interval cancer.

The Mammography Quality Standards Act and interventional mammography procedures.

The Food and Drug Administration (FDA) is in the early stages of developing regulations regarding mammographic interventional procedures. When implemented, the regulations have a significant impact on the way these procedures are performed. As part of the development process, the FDA is working with the American College of Surgeons (ACS), the American College of Radiology (ACR), and other interested professional and consumer groups. The goal is to ensure access to high-quality services for the diagnosis of breast cancer.

Sonography vs. excretory urography in acute flank pain.

A prospective study compared the diagnostic accuracy of sonography and excretory urography in determining the cause of acute flank pain in 61 patients. Forty-one patients had urinary tract stone disease. Of these, five had nonobstructing renal stones and 36 had obstructing stones. A correct diagnosis was made by urography in 85% and by sonography in 66%. Small stones at the ureterovesical junction were more accurately diagnosed by sonography (79%) than by urography (68%). In all the patients where sonography failed to detect the offending stone, the stone was calcified and evident on the plain radiographs. There were no false-positive diagnoses in the patients clinically judged to have passed a renal stone (nine patients) or whose pain was arising outside of the urinary tract (five patients). Neither sonography (17%) nor urography (50%) was accurate in diagnosing acute pyelonephritis in the six patients with this diagnosis. Although sonography is not as accurate overall as urography in acute flank pain, it is a viable alternative in those with recurrent renal colic due to stone disease and in the pregnant patient.

Percutaneous nephroureteral drainage and stenting for postsurgical ureteral leaks.

Five patients with postoperative ureteral fistulae subsequent to surgically created ureteral anastomoses were treated successfully by temporary percutaneous nephroureteral drainage and stenting. Low, constant suction applied to the drainage tubes achieved total urinary diversion, while concomitant ureteral stenting seemed to prevent subsequent stricture formation. The techniques have reduced considerably the morbidity of this particular postoperative complication.

Eight-minute excretory urographic film: once is enough.

A film reading exercise was developed to test the advisability and accuracy of using one "postinfusion" roentgenogram instead of a series of films for a complete antegrade urographic evaluation. The experience of the radiologist making the interpretations was also considered. In most cases a singly eight-minute postinfusion delayed film showed enough detail to rule out pathology when none existed and adequately revealed either specific abnormal findings or suggested an abnormality existed when such was indeed present. No false negative call was made by and of the radiologists, but experience did aid in detailing the pathology.