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David F Ransohoff

Publications and source records attributed to David F Ransohoff.

At least 19 recordsLinked to original sources
PubMed2005

Lessons from controversy: ovarian cancer screening and serum proteomics.

In 2002 a study reported that a blood test, based on pattern-recognition proteomics mass spectroscopy analysis of serum, was nearly 100% sensitive and specific to detect ovarian cancer. Plans to introduce a commercial screening test by early 2004 were delayed amid concerns about whether the approach was reproducible and reliable. In this issue of JNCI, two commentaries discuss whether the initial results are reproducible and whether bias may account for results. This essay describes how threats to validity from chance and bias may cause erroneous results and inflated expectations in the kind of observational research being conducted in several "-omics" fields to assess molecular markers for diagnosis and prognosis of cancer. To address such threats and to realize the potential of new -omics technology will require application of appropriate rules of evidence in the design, conduct, and interpretation of clinical research about molecular markers.

Biomarkers, Tumor↗
PubMed2005

A national survey of primary care physicians' methods for screening for fecal occult blood.

BACKGROUND: Screening with the fecal occult blood test (FOBT) has been shown to reduce colorectal cancer incidence and mortality in randomized, controlled trials. Although the test is simple, implementation requires adherence to specific techniques of testing and follow-up of abnormal results. OBJECTIVE: To examine how FOBT and follow-up are conducted in community practice across the United States. DESIGN: Cross-sectional national surveys of primary care physicians and the public. SETTING: The Survey of Colorectal Cancer Screening Practices in Health Care Organizations and the 2000 National Health Interview Survey. PARTICIPANTS: 1147 primary care physicians who ordered or performed FOBT and 11 365 adults 50 years of age or older who responded to questions about FOBT use. MEASUREMENTS: Self-reported data on details of FOBT implementation and follow-up of positive results. RESULTS: Although screening guidelines recommend home tests, 32.5% (95% CI, 29.8% to 35.3%) of physicians used only the less accurate method of single-sample in-office testing; another 41.2% (CI, 38.3% to 44.0%) used both types of test. Follow-up of positive test results showed considerable nonadherence to guidelines, with 29.7% (CI, 27.1% to 32.4%) of physicians recommending repeating FOBT. Furthermore, sigmoidoscopy, rather than total colon examination, was commonly recommended to work up abnormal findings. Nearly one third of adults who reported having FOBT said they had only an in-office test, and nearly one third of those who reported abnormal FOBT results reported no follow-up diagnostic procedures. LIMITATIONS: The study was based on self-reports. Data from the National Health Interview Survey may underestimate the prevalence of in-office testing and inadequate follow-up. CONCLUSIONS: Mortality reductions demonstrated with FOBT in clinical trials may not be realized in community practice because of the common use of in-office tests and inappropriate follow-up of positive results. Education of providers and system-level interventions are needed to improve the quality of screening implementation.

Colorectal Neoplasms↗
PubMed2005

Bias as a threat to the validity of cancer molecular-marker research.

Claims that molecular markers can accurately diagnose cancer have recently been disputed; some prominent results have not been reproduced and bias has been proposed to explain the original observations. As new '-omics' fields are explored to assess molecular markers for cancer, bias will increasingly be recognized as the most important 'threat to validity' that must be addressed in the design, conduct and interpretation of such research.

Animals↗
PubMed2004

Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population.

BACKGROUND: Although fecal occult-blood testing is the only available noninvasive screening method that reduces the risk of death from colorectal cancer, it has limited sensitivity. We compared an approach that identifies abnormal DNA in stool samples with the Hemoccult II fecal occult-blood test in average-risk, asymptomatic persons 50 years of age or older. METHODS: Eligible subjects submitted one stool specimen for DNA analysis, underwent standard Hemoccult II testing, and then underwent colonoscopy. Of 5486 subjects enrolled, 4404 completed all aspects of the study. A subgroup of 2507 subjects was analyzed, including all those with a diagnosis of invasive adenocarcinoma or advanced adenoma plus randomly chosen subjects with no polyps or minor polyps. The fecal DNA panel consisted of 21 mutations. RESULTS: The fecal DNA panel detected 16 of 31 invasive cancers, whereas Hemoccult II identified 4 of 31 (51.6 percent vs. 12.9 percent, P=0.003). The DNA panel detected 29 of 71 invasive cancers plus adenomas with high-grade dysplasia, whereas Hemoccult II identified 10 of 71 (40.8 percent vs. 14.1 percent, P<0.001). Among 418 subjects with advanced neoplasia (defined as a tubular adenoma at least 1 cm in diameter, a polyp with a villous histologic appearance, a polyp with high-grade dysplasia, or cancer), the DNA panel was positive in 76 (18.2 percent), whereas Hemoccult II was positive in 45 (10.8 percent). Specificity in subjects with negative findings on colonoscopy was 94.4 percent for the fecal DNA panel and 95.2 percent for Hemoccult II. CONCLUSIONS: Although the majority of neoplastic lesions identified by colonoscopy were not detected by either noninvasive test, the multitarget analysis of fecal DNA detected a greater proportion of important colorectal neoplasia than did Hemoccult II without compromising specificity.

Adenocarcinoma↗
PubMed2004

Are physicians doing too much colonoscopy? A national survey of colorectal surveillance after polypectomy.

BACKGROUND: Increasing use of colonoscopy for colorectal cancer screening and surveillance of colorectal adenomas after polypectomy has given rise to concerns about the availability of endoscopic resources in the United States. Guidelines recommend surveillance after polypectomy at 3 to 5 years for a small adenoma, and follow-up is not advised for hyperplastic polyps. The intensity of physicians' surveillance is largely unstudied. OBJECTIVE: To survey practicing gastroenterologists and general surgeons about their perceived need for the frequency of surveillance after polypectomy, to compare survey responses to practice guidelines, and to identify factors influencing their recommendations for surveillance. DESIGN: Survey study conducted by the National Cancer Institute. SETTING: A nationally representative study of physicians in the United States. PARTICIPANTS: 349 gastroenterologists and 316 general surgeons. MEASUREMENTS: Questionnaires mailed in 1999 and 2000 assessed physicians' recommendations for surveillance after polypectomy in asymptomatic, average-risk patients. RESULTS: Response rates were 83%. Among gastroenterologists (317 of 349) and surgeons (125 of 316) who perform screening colonoscopy, 24% (95% CI, 19.3% to 28.7%) of gastroenterologists and 54% (CI, 44.9% to 62.5%) of surgeons recommend surveillance for a hyperplastic polyp. For a small adenoma, most physicians recommended surveillance colonoscopy and more than 50% recommended examinations every 3 years or more often. Physicians indicated that published evidence was very influential in their practice (83% [CI, 78.8% to 87.2%] of gastroenterologists and 78% [CI, 72.5% to 86.8%] of surgeons). By contrast, only half of respondents reported that guidelines were very influential. LIMITATIONS: The study was based on physicians' self-reported practice patterns. Results may overestimate or underestimate the performance of surveillance colonoscopy. CONCLUSIONS: Some surveillance colonoscopy seems to be inappropriately performed and in excess of guidelines, particularly for hyperplastic polyps and low-risk lesions such as a small adenoma. These results suggest unnecessary demand for endoscopic resources.

Adenoma↗
PubMed2004

Interpretations of 'appropriate' minority inclusion in clinical research.

The range of possible interpretations of the phrase "appropriate representation" has left investigators struggling with the practical application of the National Institutes of Health guidelines on the inclusion of minorities in research. At least three goals might be reached by including minorities in clinical research: to test specific hypotheses about differences by race and ethnicity; to generate hypotheses about possible differences by race and ethnicity; and to ensure the just distribution of the benefits and burdens of participation in research, regardless of whether there are expected differences in outcome by race or ethnicity. In this paper, we describe possible interpretations of "appropriate representation," as well as provide a general approach that investigators might use to address this issue. To expand scientific knowledge about the health of minority populations, investigators should be expected to state which goal they have selected and why that goal is appropriate as compared with other possible goals.

Clinical Trials as Topic↗
PubMed2003

Using risk for advanced proximal colonic neoplasia to tailor endoscopic screening for colorectal cancer.

BACKGROUND: Colonoscopic screening for colorectal cancer has been suggested because sigmoidoscopy misses nearly half of persons with advanced proximal neoplasia. OBJECTIVE: To create a clinical index to stratify risk for advanced proximal neoplasia and to identify a subgroup with very low risk in which screening sigmoidoscopy alone might suffice. DESIGN: Cross-sectional study. SETTING: A company-based program of screening colonoscopy for colorectal cancer. PATIENTS: Consecutive persons 50 years of age or older undergoing first-time screening colonoscopy between September 1995 and June 2001. MEASUREMENTS: A clinical index with 3 variables was created from information on the first 1994 persons. Points were assigned to categories of age, sex, and distal findings. Risk for advanced proximal neoplasia (defined as an adenoma 1 cm or larger or one with villous histology, severe dysplasia, or cancer) was measured for each score. The index was tested on the next 1031 persons from the same screening program. RESULTS: Of 1994 persons, 67 (3.4%) had advanced proximal neoplasia. A low-risk subgroup comprising 37% of the cohort had scores of 0 or 1 and a risk of 0.68% (95% CI, 0.22% to 1.57%). Among the validation group of 1031 persons, risk for advanced proximal neoplasia in the low-risk subgroup (comprising 47% of the cohort) was 0.4% (upper confidence limit of 1.49%). Application of this index detected 92% of persons with advanced proximal neoplasms and, if applied following screening sigmoidoscopy, could reduce the need for colonoscopy by 40%. The marginal benefit of colonoscopy among low-risk persons was small: To detect 7 additional persons with advanced proximal neoplasia, 1217 additional colonoscopies would be required. CONCLUSIONS: This clinical index stratifies the risk for advanced proximal neoplasia and identifies a subgroup at very low risk. If it is validated in other cohorts or groups, the index could be used to tailor endoscopic screening for colorectal cancer.

Age Distribution↗
PubMed2003

International variation in screening mammography interpretations in community-based programs.

BACKGROUND: Variations in mammography interpretations may have important clinical and economic implications. To evaluate international variability in mammography interpretation, we analyzed published reports from community-based screening programs from around the world. METHODS: A total of 32 publications were identified in MEDLINE that fit the study inclusion criteria. Data abstracted from the publications included features of the population screened, examination technique, and clinical outcomes, including the percentage of mammograms judged to be abnormal, positive predictive value of an abnormal mammogram (PPV(A)), positive predictive value of a biopsy performed (PPV(B)), and percentages of breast cancer patients with ductal carcinoma in situ (DCIS) and minimal disease (DCIS and/or tumor size < or =10 mm). North American screening programs were compared with those from other countries using meta-regression analysis. All statistical tests were two-sided. RESULTS: Wide ranges were noted for the percentage of mammograms judged to be abnormal (1.2%-15.0%), for PPV(A) (3.4%-48.7%), for PPV(B) (5.0%-85.2%), for percentage diagnosed with DCIS (4.3%-68.1%), and for percentage diagnosed with minimal disease (14.0%-80.6%). The percentage of mammograms judged to be abnormal were 2-4 percentage points higher in North American screening programs than they were in programs from other countries, after adjusting for covariates such as percentage of women who were less than 50 years of age and calendar year in which the mammogram was performed. The percentage of mammograms judged to be abnormal had a negative association with PPV(A) and PPV(B) (both P<.001) and a positive association with the frequency of DCIS cases diagnosed (P =.008) and the number of DCIS cases diagnosed per 1000 screens (P =.024); no consistent relationship was observed with the proportion of breast cancer diagnoses reported as having minimal disease or the number of minimal disease cases diagnosed per 1000 screens. CONCLUSION: North American screening programs appear to interpret a higher percentage of mammograms as abnormal than programs from other countries without evident benefit in the yield of cancers detected per 1000 screens, although an increase in DCIS detection was noted.

Aged↗