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Ruth Etzioni

Publications and source records attributed to Ruth Etzioni.

15 recordsLinked to original sources
PubMed2026

Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans↗
PubMed2003

Polymorphic markers in the 5alpha-reductase type II gene and the incidence of prostate cancer.

In the prostate, the enzyme encoded by the SRD5A2 gene (5alpha-reductase) converts testosterone to dihydrotestosterone, a potent androgen that has been hypothesized to play a role in the genesis of prostate cancer. Several polymorphisms have been identified in the SRD5A2 gene, including a valine-to-leucine substitution (V89L) at codon 89, a variable number of TA dinucleotide repeats and a missense substitution at codon 49 resulting in an amino acid substitution of alanine with threonine (A49T). To investigate the influence of these polymorphisms on prostate cancer risk, we conducted a case-control study nested within the Beta-Carotene and Retinol Efficacy Trial. Genotypes were determined by PCR-based capillary electrophoresis using genomic DNA isolated from 300 cases and 300 controls matched on the basis of race, age at enrollment (within 5 years), enrollment study center and year of randomization. There was no association between V89L genotypes and prostate cancer risk. The age- and race-adjusted odds ratio (OR) associated with the VL and LL genotypes were 1.06 (95% confidence interval (CI) = 0.75-1.49) and 0.99 (95% CI = 0.57-1.73), respectively, as compared to the VV genotype. The age- and race-adjusted odds ratio for men having 1 TA(9) or TA(18) allele was 0.98 (95% CI = 0.64-1.48) when compared to men without TA repeats. The corresponding odds ratio for men without the TA(0) alleles was 0.68 (95% CI = 0.21-2.19). The age- and race-adjusted odds ratio associated with having at least 1 T allele at codon 49 was 1.11 (95% CI = 0.58-2.11), as compared to the AA genotype. Our results do not support the hypothesis that the V89L and A49T polymorphisms in the SRD5A2 gene are related to the risk of prostate cancer, but are compatible with the suggestion from earlier studies that men who are homozygous for the TA(9) or (18) alleles and men who have the TA(9)/TA(18) genotype are at a modestly reduced risk.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

Cost effectiveness of lung-volume-reduction surgery for patients with severe emphysema.

BACKGROUND: The National Emphysema Treatment Trial, a randomized clinical trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema, included a prospective economic analysis. METHODS: After pulmonary rehabilitation, 1218 patients at 17 medical centers were randomly assigned to lung-volume-reduction surgery or continued medical treatment. Costs for the use of medical care, medications, transportation, and time spent receiving treatment were derived from Medicare claims and data from the trial. Cost effectiveness was calculated over the duration of the trial and was estimated for 10 years of follow-up with the use of modeling based on observed trends in survival, cost, and quality of life. RESULTS: Interim analyses identified a group of patients with excess mortality and little chance of improved functional status after surgery. When these patients were excluded, the cost-effectiveness ratio for lung-volume-reduction surgery as compared with medical therapy was 190,000 dollars per quality-adjusted life-year gained at 3 years and 53,000 dollars per quality-adjusted life-year gained at 10 years. Subgroup analyses identified patients with predominantly upper-lobe emphysema and low exercise capacity after pulmonary rehabilitation who had lower mortality and better functional status than patients who received medical therapy. The cost-effectiveness ratio in this subgroup was 98,000 dollars per quality-adjusted life-year gained at 3 years and 21,000 dollars at 10 years. Bootstrap analysis revealed substantial uncertainty for the subgroup and 10-year estimates. CONCLUSIONS: Given its cost and benefits over three years of follow-up, lung-volume-reduction surgery is costly relative to medical therapy. Although the predictions are subject to substantial uncertainty, the procedure may be cost effective if benefits can be maintained over time.

Cost-Benefit Analysis↗
PubMed2003

The case for early detection.

Early detection represents one of the most promising approaches to reducing the growing cancer burden. It already has a key role in the management of cervical and breast cancer, and is likely to become more important in the control of colorectal, prostate and lung cancer. Early-detection research has recently been revitalized by the advent of novel molecular technologies that can identify cellular changes at the level of the genome or proteome, but how can we harness these new technologies to develop effective and practical screening tests?

Biomarkers, Tumor↗
PubMed2003

Cancer-attributable costs of diagnosis and care for persons with screen-detected versus symptom-detected colorectal cancer.

BACKGROUND & AIMS: Colorectal cancer screening is effective and cost-effective, but little data from health plan settings are available inform decision-makers regarding direct economic implications of colorectal cancer screening programs. The purpose of this study was to compare the prediagnosis evaluation and first-year treatment costs of persons diagnosed with colorectal cancer, stratified by whether the cancer was detected by screening using fecal occult blood testing or evaluation of symptoms. METHODS: This retrospective study analyzed persons diagnosed with colorectal cancer from 1993 to 1999 in Group Health Cooperative, a large health maintenance organization in Washington state. Total health care costs during 3 months before and 12 months following diagnosis were compared for screen-detected versus symptom-detected individuals. RESULTS: During this time, 206 cancers were detected by screening and 717 by symptoms. In the 3 months before diagnosis, total costs were 7346 US dollars for persons with screen-detected versus 10,042 US dollars for those with symptom-detected cancer (P < 0.01). Stratified by stage, diagnosis costs were significantly lower for persons with stage B cancer (7282 US dollars vs. 11,682 US dollars ; P < 0.01) and nonsignificantly lower for other stages. A total of 53% of screen-detected cases were Dukes' stage A or in situ at diagnosis versus 30% of symptom-detected cases (P < 0.01). Overall costs were lower for the screen-detected group in the 12 months following diagnosis (22,369 US dollars vs. 29,471 US dollars; P < 0.01). CONCLUSIONS: Colorectal cancer screening can substantially reduce prediagnosis evaluation costs. These savings are of interest to health plans and should be factored into cost-effectiveness evaluations of screening programs.

Aged↗
PubMed2003

Combining biomarkers to detect disease with application to prostate cancer.

In early detection of disease, combinations of biomarkers promise improved discrimination over diagnostic tests based on single markers. An example of this is in prostate cancer screening, where additional markers have been sought to improve the specificity of the conventional Prostate-Specific Antigen (PSA) test. A marker of particular interest is the percent free PSA. Studies evaluating the benefits of percent free PSA reflect the need for a methodological approach that is statistically valid and useful in the clinical setting. This article presents methods that address this need. We focus on and-or combinations of biomarker results that we call logic rules and present novel definitions for the ROC curve and the area under the curve (AUC) that are applicable to this class of combination tests. Our estimates of the ROC and AUC are amenable to statistical inference including comparisons of tests and regression analysis. The methods are applied to data on free and total PSA levels among prostate cancer cases and matched controls enrolled in the Physicians' Health Study.

Aged↗
PubMed2003

Endogenous sex hormones and prostate cancer risk: a case-control study nested within the Carotene and Retinol Efficacy Trial.

To examine whether endogenous androgens influence the occurrence of prostate cancer, we conducted a nested case-control study among participants enrolled in the Carotene and Retinol Efficacy Trial. We analyzed serum samples of 300 cases diagnosed between 1987 and 1998, and 300 matched controls. Higher concentrations of testosterone (T) were not associated with increased prostate cancer risk. Relative to men with levels in the lowest fourth of the distribution, men in the upper fourth of total T had a risk of 0.82 [95% confidence interval (CI), 0.52-1.29]. The corresponding relative risks for free T (0.72; 95% CI, 0.45-1.14), percentage of free T (0.74; 95% CI, 0.46-1.19), and total T:sex hormone binding globulin ratio (0.52; 95% CI, 0.32-0.83) similarly were not elevated. Higher concentrations of androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were weakly associated with risk. Relative risks associated with being in the highest fourth for androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were 1.20 (95% CI, 0.76-1.89), 1.38 (95% CI, 0.86-2.21), and 1.27 (95% CI, 0.80-2.00), respectively. Men in the upper fourth of total estradiol (E2), free E2 and percentage of free E2 had relative risks of 0.71 (95% CI, 0.42-1.13), 0.52 (95% CI, 0.33-0.82), and 0.65 (95% CI, 0.40-1.05), respectively. The inverse association between E2 and prostate cancer risk was largely restricted to men with blood collection within 3 years of diagnosis. Our results add to the evidence that serum testosterone is unrelated to prostate cancer incidence. The suggestions that intraprostatic androgen activity may increase risk and that serum estrogens may decrease risk, warrant additional study.

Age Distribution↗
PubMed2002

Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends.

BACKGROUND: Overdiagnosis of clinically insignificant prostate cancer is considered a major potential drawback of prostate-specific antigen (PSA) screening. Quantitative estimates of the magnitude of this problem are, however, lacking. We estimated rates of prostate cancer overdiagnosis due to PSA testing that are consistent with the observed incidence of prostate cancer in the United States from 1988 through 1998. Overdiagnosis was defined as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. METHODS: We developed a computer simulation model of PSA testing and subsequent prostate cancer diagnosis and death from prostate cancer among a hypothetical cohort of two million men who were 60-84 years old in 1988. Given values for the expected lead time--that is, the time by which the test advanced diagnosis--and the expected incidence of prostate cancer in the absence of PSA testing, the model projected the increase in population incidence of prostate cancer associated with PSA testing. By comparing the model-projected incidence with the observed incidence derived from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry data, we determined the lead times and corresponding overdiagnosis rates that were consistent with the observed data. RESULTS: SEER data on prostate cancer incidence from 1988 through 1998 were consistent with overdiagnosis rates of approximately 29% for whites and 44% for blacks among men with prostate cancers detected by PSA screening. CONCLUSIONS: Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing.

Aged↗
PubMed2002

Prostate-specific antigen testing in black and white men: an analysis of medicare claims from 1991-1998.

OBJECTIVES: To describe the trends in prostate-specific antigen (PSA) use and associated cancer detection among black and white Medicare beneficiaries older than 65 years during the calendar period from January 1991 through December 1998. METHODS: Medicare claims data were linked with cancer registry data from the Surveillance, Epidemiology and End Results program of the National Cancer Institute. Data from a 5% random sample of men without a diagnosis of prostate cancer were combined with data from prostate cancer cases diagnosed during the calendar period from 1991 to 1998. PSA tests conducted after a diagnosis of prostate cancer were excluded. RESULTS: PSA use has stabilized among white men, reaching an annual rate of 38% by 1995 and remaining at this level through 1998. The annual rate of use among black men reached 31% by 1998, but was still increasing at that time. By 1996, at least 80% of tests in both blacks and whites were second or later tests. By the end of 1996, 35% of white men and 25% of black men were undergoing testing at least biannually or more frequently. In 1996, 83% of diagnoses in whites and 77% in blacks were preceded by a PSA test. CONCLUSIONS: Older black men lag slightly behind older white men in their use of the PSA test; however, annual testing rates in blacks have yet to stabilize. In both race groups, an overwhelming majority of diagnoses are associated with a PSA test, whether for screening or diagnostic purposes. Regular screening rates in blacks are substantially lower than in whites, but the regular screening rates are relatively low in both race groups. Should PSA screening prove efficacious, efforts to promote regular use among both black and white men will likely be needed.

Black or African American↗
PubMed2002

Estimating the influence of rescreening interval on the benefits associated with cancer screening: approaches and limitations.

ABSTRACT Randomized controlled trials that seek to measure the ability of a screening test to lower cancer mortality generally do not provide data that bear on the relative efficacy of different screening intervals. Guidance regarding the choice of a screening interval that achieves a high level of case-finding, without being excessively costly, can be obtained from one or more of several study designs that examine the subsequent occurrence of cancer in persons who have had a negative screening test. However, each of these can potentially provide a misleading result, and so their limitations must be considered before using the data they generate to develop a rational rescreening policy.

False Negative Reactions↗
PubMed2002

Estimating health care costs related to cancer treatment from SEER-Medicare data.

BACKGROUND: Cancer-specific medical care costs are used by health service researchers, medical decision analysts, and health care policymakers. The SEER-Medicare database is a unique data resource that makes it possible to derive incidence- and prevalence-based estimates of cancer-related medical care costs by site and stage of disease, by treatment approach, and for age and gender strata for individuals older than 65 years. OBJECTIVES: This paper describes the cost-related data available in the SEER-Medicare database, and discusses techniques and methods that have been used to derive various cost estimates from these data. The limitations of SEER-Medicare data as a source of cost estimates are also discussed. RESULTS: Examples of cost estimates for colorectal and breast cancer derived from SEER-Medicare are presented, including estimates of incidence-based cost (average cost per patient) by the initial, terminal, and continuing care phases of cancer treatment. Estimates of cancer-related treatment costs, costs by type of treatment, and long-term costs are presented, as are prevalence-based costs (aggregate Medicare and national expenditures) by cancer type.

Aged↗
PubMed2002

Lifetime cancer-attributable cost of care for long term survivors of colorectal cancer.

OBJECTIVES: We aimed to determine cancer-related medical care costs for long term survivors of colorectal cancer. METHODS: The SEER-Medicare database was used to measure lifetime cancer-attributable costs of care for those with colorectal cancer surviving at least 5 yr versus age- and gender-matched controls. Costs were directly estimated, stratified by age at diagnosis and stage at diagnosis, for years 6-11 after diagnosis and then modeled to estimate lifetime costs. Cost differences between cancer cases and controls were compared to expected costs based on published guidelines for postcancer surveillance. RESULTS: Lifetime medical costs for long term survivors (future years not discounted) were up to $19,516 higher than control costs, and were highest for younger age groups and those with early-stage disease. Excess costs for cancer survivors exceeded expected surveillance costs by $2,223-8,822 for years 6-10 from the date of initial diagnosis. CONCLUSIONS: Cancer-attributable medical costs can be substantial for long term survivors, and exceed expected costs of surveillance. Future research is need to determine the components of excess cost in this survivor group.

Age Factors↗
PubMed2002

Measuring costs: administrative claims data, clinical trials, and beyond.

BACKGROUND: Accurate estimation of medical care costs raises a host of issues, both practical and methodological. OBJECTIVES: This article reviews methods for estimating the long-term medical care costs associated with a cancer diagnosis. METHODS: The authors consider data from administrative claims databases and describe the analytic challenges posed by these increasingly common resources. They present a number of statistical methods that are valid under censoring and describe methods for estimating mean costs and controlling for covariates. In addition, the authors compare two different approaches for estimating the cancer-related costs; namely, the portion of the long-term costs that may be attributed to the disease. Examples from economic studies of breast and colorectal cancer are presented. RESULTS: In an analysis of data on colorectal cancer costs from the SEER-Medicare database, the two methods used to estimate expected long-term costs (one model based, one not model-based) yielded similar results. However, in calculating expected cancer-related costs, a method that included future medical costs among controls yielded quite different results from the method that did not include these future costs. CONCLUSIONS: Statistical methods for analyzing long-term medical costs under censoring are available and appropriate in many applications where total or disease-related costs are of interest. Several of these approaches are nonparametric and therefore may be expected to be robust against the non-standard features that are often encountered when analyzing medical cost data.

Clinical Trials as Topic↗
PubMed2002

Androgen receptor polymorphisms and the incidence of prostate cancer.

The human androgen receptor gene contains polymorphic CAG and GGC repeats in exon 1. We investigated whether the number of CAG and/or GGC repeats is related to prostate cancer risk in a case-control study nested within the beta Carotene and Retinol Efficacy Trial. Among 300 cases and 300 controls, we did not observe any increase in risk associated with fewer CAG or GGC repeats. We observed a nonsignificant decrease in risk associated with each unit of decrease in CAG length [odds ratio (OR), 0.98; 95% confidence interval (CI), 0.93-1.03). Men with CAG <22 had a relative risk of prostate cancer of 0.89 (95% CI, 0.65-1.23) compared with men with CAG > or =22. There was no appreciable difference in the mean number of GGC repeats between cases and controls; the estimated change in the risk of prostate cancer associated with one fewer GGC repeat was 0.97 (95% CI, 0.88-1.06). The risk in men at or below the mean number of GGC repeats (17) was 0.80 (95% CI, 0.57-1.12). In contrast to prior reports, men with both short CAG (<22) and short GGC (< or =17) repeats were not at increased risk of prostate cancer (OR, 0.56; 95% CI, 0.32-0.98), compared with men with > or =22 CAG repeats and >17 GGC repeats. Our results do not support the hypothesis that a small number of CAG or GGC repeats in the androgen receptor gene increases a man's risk of prostate cancer.

Aged↗