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R Etzioni

Publications and source records attributed to R Etzioni.

At least 19 recordsLinked to original sources

Cost-effectiveness of microsatellite instability screening as a method for detecting hereditary nonpolyposis colorectal cancer.

BACKGROUND: The National Cancer Institute has published consensus guidelines for universal screening for hereditary nonpolyposis colorectal cancer (HNPCC) in patients with newly diagnosed colorectal cancer. OBJECTIVE: To determine the cost-effectiveness of screening compared with standard care in eligible patients with colorectal cancer and their siblings and children. DESIGN: Cost-effectiveness analysis. DATA SOURCES: National colorectal cancer registry data, the Creighton International Hereditary Colorectal Cancer Registry, Medicare claims records, and published literature. TARGET POPULATION: Patients with newly diagnosed colorectal cancer and their siblings and children. TIME HORIZON: Lifetime (varies depending on age at screening). PERSPECTIVE: Societal. INTERVENTIONS: Initial office-based screening to determine eligibility (based on personal and family cancer history), followed by tumor testing for microsatellite instability. Those with microsatellite instability were offered genetic testing for HNPCC. Siblings and children of patients with cancer and the HNPCC mutation were offered genetic testing, and those who were found to carry the mutation received lifelong colorectal cancer screening. MEASUREMENTS: Life-years gained. RESULTS OF BASE-CASE ANALYSIS: When only the patients with cancer were considered, cost-effectiveness of screening was $42 210 per life-year gained. When patients with cancer and their siblings and children were considered together, cost-effectiveness increased to $7556 per life-year gained. RESULTS OF SENSITIVITY ANALYSIS: The model was most sensitive to the estimated survival gain from screening siblings and children, to the prevalence of HNPCC mutations among patients with newly diagnosed cancer, and to the discount rate. In probabilistic analysis, the 90% CI for the cost-effectiveness of screening patients with cancer plus their relatives was $4874 to $21 576 per life-year gained. CONCLUSION: Screening patients with newly diagnosed colorectal cancer for HNPCC is cost-effective, especially if the benefits to their immediate relatives are considered.

Age Distribution↗

The impact of including future medical care costs when estimating the costs attributable to a disease: a colorectal cancer case study.

A source of controversy in the economic literature concerns whether to include or exclude future medical care costs when computing attributable costs for lifesaving interventions. Although it is hypothesized that including future medical care costs will offset the cost savings achieved through prevention, the magnitude of the effect is not known. The objectives of the present study are to develop a methodology for estimating the excess costs of care among colorectal cancer patients, including and excluding future costs of care, and comparing these results with previous studies that do not include costs in added years of life. Subjects in the study included those identified with colorectal cancer drawn from the Surveillance, Epidemiology and End Results (SEER)-Medicare database and an age- and gender-matched control group drawn from the general Medicare population. Using the Kaplan-Meier Sample Average estimator, we directly estimate expected 11-year costs, and then, with the addition of some simple extrapolating assumptions, determine expected 25-year costs. The latter time horizon captures lifetime costs for over 90% of the cohort. Males results for discounted, stage-specific 11- versus 25-year excess costs: in situ, 22411 dollars versus 23494 dollars; Stage 1, 29365 dollars versus 32510 dollars; Stage 2, 28114 dollars versus 25263 dollars; Stage 3, 27397 dollars versus 19647 dollars; Stage 4, 3006 dollars versus 7837 dollars. Trends were similar for females. It can be concluded that adding costs of care in future years for those whose colorectal cancer is prevented owing to screening greatly alters the estimate of lifetime excess costs for colorectal cancer patients, and can produce negative results for advanced stage disease. The results emphasize the need to adopt a standard approach for dealing with future costs when evaluating lifesaving interventions for cost-effectiveness analyses.

Cohort Studies↗

Serial prostate specific antigen, free-to-total prostate specific antigen ratio and complexed prostate specific antigen for the diagnosis of prostate cancer.

PURPOSE: The free-to-total prostate specific antigen (PSA) ratio and complexed PSA have been introduced as adjuncts to total PSA for prostate cancer screening. Little data exist on the use of these tests for serial PSA screening. We compared serial total PSA, the free-to-total PSA ratio and calculated complexed PSA in men diagnosed with prostate cancer and matched controls in a population based study. MATERIALS AND METHODS: We identified 90 men diagnosed with prostate cancer between 1988 and 1996 with at least 3 serial serum samples obtained at 2-year intervals who were participants in the beta-Carotene and Retinol Efficacy Trial for the prevention of lung cancer. Samples were available up to 10 years before diagnosis. A total of 90 age matched men from the same cohort without prostate carcinoma were identified as controls. Free and total PSA was measured by the Abbott AxSYM system. RESULTS: Baseline demographics of cases and controls were similar. At baseline and diagnosis the men with prostate cancer had higher total and complexed PSA, and a lower free-to-total PSA ratio than controls. Mean followup was 5.2 years in cases and 5.5 in controls. The yearly change in PSA parameters in cases versus controls was 20.7% versus 3.5% for total, -3.4% versus 0.2% for free-to-total and 21.5% versus 3.4% for complexed PSA (p <0.0001). At diagnosis PSA alone was estimated to perform with more than 90% specificity in our model. CONCLUSIONS: In this population based study total PSA was superior to the free-to-total PSA ratio for predicting the development of prostate cancer. While serial changes in free-to-total PSA ratios with time were statistically significantly different in men diagnosed with prostate cancer and controls, the magnitude of these serial changes were slight enough to render them clinically insignificant.

Adenocarcinoma↗

Quality of life in survivors of colorectal carcinoma.

BACKGROUND: Colon carcinoma is a common malignancy that accounts for a substantial share of all cancer-related morbidity and mortality. However, little is known with regard to general and disease specific quality of life in survivors of colorectal carcinoma, particularly from community-based samples of cases across stage and survival times from diagnosis. METHODS: Subjects with colorectal carcinoma were recruited from the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry. Subjects completed two self-administered surveys: the Functional Assessment of Cancer Therapy Scales for Colorectal Cancer (FACT-C) and the Health Utilities Index (HUI) Mark III. RESULTS: One hundred seventy-three respondents (average age: 70.4 years, 71.4% female) completed the survey. In the first 3 years after diagnosis, quality of life was lower and varied substantially among respondents. After 3 years, respondents in all TNM stages of disease except Stage IV reported a relatively uniform and high quality of life. Pain, functional well-being, and social well-being were affected most substantially across all stages and times from diagnosis. Low income status was associated with worse outcomes for pain, ambulation, and social and emotional well-being. Only emotional well-being scores improved significantly over time in both surveys. CONCLUSIONS: Those individuals who achieve a long term remission from colorectal carcinoma may experience a relatively high quality of life, although deficits remain for several areas, particularly in those of low socioeconomic status. Sampling design may have excluded the most severely ill patients.

Activities of Daily Living↗

The effectiveness of mammography promotion by volunteers in rural communities.

INTRODUCTION: The Community Trial of Mammography Promotion assessed the effectiveness of mammography promotion by community volunteer groups in rural areas. Three interventions were tested. One used an individual counseling strategy, one used a community activities strategy, and a third combined the two strategies. METHODS: The effects of the interventions were tested by randomizing 40 communities either to the study interventions or to a control group. A cohort of 352 women from each community was randomly selected and used to evaluate the interventions' effectiveness. Of these, 6592 women were eligible for screening mammography at baseline and follow-up and were successfully interviewed prior to and after study intervention activities. RESULTS: Although the interventions did not significantly increase women's overall use of mammography, the community activities intervention increased use at follow-up by regular users over baseline by 2.9% (p = 0.01). Intervention appears to have increased the use of mammography among certain groups of women who were not regular users at baseline, including those in communities without female physicians (10% to 16%; p < 0.05), and among women with no health insurance (10% to 23%; p </= 0.05). CONCLUSION: Volunteers can effectively promote mammography in rural communities.

Adult↗

Simulation modeling of outcomes and cost effectiveness.

Modeling will continue to be used to address important issues in clinical practice and health policy issues that have not been adequately studied with high-quality clinical trials. The apparent ad hoc nature of models belies the methodologic rigor that is applied to create the best models in cancer prevention and care. Models have progressed from simple decision trees to extremely complex microsimulation analyses, yet all are built using a logical process based on objective evaluation of the path between intervention and outcome. The best modelers take great care to justify both the structure and content of the model and then test their assumptions using a comprehensive process of sensitivity analysis and model validation. Like clinical trials, models sometimes produce results that are later found to be invalid as other data become available. When weighing the value of models in health care decision making, it is reasonable to consider the alternatives. In the absence of data, clinical policy decisions are often based on the recommendations of expert opinion panels or on poorly defined notions of the standard of care or medical necessity. Because such decision making rarely entails the rigorous process of data collection, synthesis, and testing that is the core of well-conducted modeling, it is usually not possible for external audiences to examine the assumptions and data that were used to derive the decisions. One of the modeler's most challenging tasks is to make the structure and content of the model transparent to the intended audience. The purpose of this article is to clarify the process of modeling, so that readers of models are more knowledgeable about their uses, strengths, and limitations.

Computer Simulation↗

Cancer surveillance series: interpreting trends in prostate cancer--part III: Quantifying the link between population prostate-specific antigen testing and recent declines in prostate cancer mortality.

BACKGROUND: The objective of this study was to investigate the circumstances under which dissemination of prostate-specific antigen (PSA) testing, beginning in 1988, could plausibly explain the declines in prostate cancer mortality observed from 1992 through 1994. METHODS: We developed a computer simulation model by use of information on population-based PSA testing patterns, cancer detection rates, average lead time (the time by which diagnosis is advanced by screening), and projected decreased risk of death associated with early diagnosis of prostate cancer through PSA testing. The model provides estimates of the number of deaths prevented by PSA testing for the 7-year period from 1988 through 1994 and projects what prostate cancer mortality for these years would have been in the absence of PSA testing. RESULTS: Results were generated by assuming a level of screening efficacy similar to that hypothesized for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Under this assumption, the projected mortality in the absence of PSA testing continued the increasing trend observed before 1991 only when it was assumed that the mean lead time was 3 years or less. Projected mortality trends in the absence of PSA screening were not consistent with pre-1991 increasing trends for lead times of 5 years and 7 years. CONCLUSIONS: When screening is assumed to be at least as efficacious as hypothesized in the PLCO trial, it is unlikely that the entire decline in prostate cancer mortality can be explained by PSA testing based on current beliefs concerning lead time. Only very short lead times would produce a decline in mortality of the magnitude that has been observed.

Black or African American↗

Reduced dose intravenous immunoglobulin does not decrease transplant-related complications in adults given related donor marrow allografts.

Graft-vs.-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Intravenous immunoglobulin (IVIg) given at a dose of 500 mg/kg/wk has been shown to decrease the risk of acute GVHD, interstitial pneumonia, and infection in adults early after allogeneic transplantation. The current study is a controlled trial to determine whether a lower total dose of IVIg given with pretransplant loading reduces the incidence of transplant-related complications. In a randomized trial of 241 patients > or =20 years of age who were given related donor marrow allografts, 121 individuals receiving Ig prophylaxis (500 mg/kg/d loading from day -6 to -1 and then 100 mg/kg every 3 days from day 3 to 90) were compared with 120 control patients who did not receive IVIg. Randomization was stratified by human leucocyte antigen-matching, remission status of malignancy, GVHD prophylaxis, and cytomegalovirus (CMV) serology. The study was powered to detect a reduction in acute GVHD by 18% and a decrease in transplant-related mortality by 17%. Pretransplant IVIg loading and posttransplant maintenance achieved median serum IgG levels >1350 mg/dL, which were approximately twofold greater than the untreated controls (p<0.01). White blood cell and platelet recoveries were similar for the two groups, although control patients required fewer units of platelets per day (2.5 vs. 3.3, p = 0.008). No significant differences in the incidence of CMV infection, interstitial pneumonia, or bacteremia were observed. The incidence of acute GVHD did not differ between the two groups; however, acute GVHD was less frequent among IVIg recipients achieving maximum serum IgG levels >3000 mg/dL (60 vs. 79%). Neither transplant-related mortality nor disease-free survival was significantly altered by Ig prophylaxis. However, the cumulative incidence of relapse of malignancy was higher in IVIg recipients than in controls (31 vs. 18%, p = 0.03). Multivariable regression analysis demonstrated a 1.89 increased relative risk of relapse for individuals given IVIg (p = 0.021). We conclude that pretransplant loading and a shorter course and lower total dose of IVIg prophylaxis did not appear to decrease the risk of acute GVHD or mortality among adults receiving related donor marrow transplants. Note, IVIg administration may be associated with an increased risk of recurrent malignancy, a finding that warrants further investigation.

Acute Disease↗

Serial prostate specific antigen screening for prostate cancer: a computer model evaluates competing strategies.

PURPOSE: We compare prostate specific antigen (PSA) screening strategies in terms of expected years of life saved with screening, number of screens, number of false-positive screens and rates of over diagnosis, defined as detection by PSA screening of patients who would never have been diagnosed without screening. MATERIALS AND METHODS: A computer model of disease progression, clinical diagnosis, PSA growth and PSA screening was used. Under baseline conditions, when screening is not considered, the model replicates clinical diagnosis and disease mortality rates recorded by the Surveillance, Epidemiology and End Results Program of the National Cancer Institute in the mid 1980s. RESULTS: Biannual screening with PSA greater than 4.0 ng./ml. was projected to reduce the number of screens and false-positive tests by almost 50% relative to annual screening while retaining 93% of years of life saved. With annual screening use of an age specific bound for PSA to consider a test positive instead of the standard 4.0 ng./ml. was projected to reduce false-positive screens by 27% and over diagnosis by a third while retaining almost 95% of years of life saved. Sensitivity analyses did not change the relative efficacy of biannual screening. CONCLUSIONS: Under the model assumptions biannual PSA screening is a cost-effective alternative to annual PSA screening for prostate cancer. With annual screening use of an age specific bound for PSA positivity appears to reduce false-positive results and over diagnosis rates sharply relative to a bound of 4 ng./ml. while retaining most of the survival benefits.

Adult↗

Community attitudes and mammography use: does it really matter what other people think?

This study examined whether community characteristics, particularly community attitudes regarding mammography use, are associated with women's use of mammography in rural communities. Forty communities in predominantly rural areas of Washington State were selected for inclusion in this study based on their size and distance from an urban center. Characteristics of the communities were assessed as were characteristics of women living in the communities. From each community, random samples of 352 women between 50 and 80 years old participated by completing a telephone survey that included questions on a variety of topics, including their use of mammography. Logistic regression analyses revealed community of residence to be a significant predictor of individual women's mammography use after adjusting for individual level predictors of mammography use including age, education, employment, marital status, financial situation, and ease of access to medical services. An examination of the influence of community characteristics revealed women living in communities with supportive community attitudes towards mammography use report higher levels of mammography use than do women living in communities with less supportive attitudes. The presence or absence of male or female physicians or of mammography facilities in a local community was not associated with statistically significant effects on women's mammography use. Community attitudes are associated with mammography use in rural communities. Public health interventions that change community attitudes may have effects that extend beyond the people directly contacted by these interventions.

Aged↗

Asymptomatic incidence and duration of prostate cancer.

Prostate cancer is known as a disease with an extremely high prevalence relative to its clinical incidence in the population. The combination of preclinical incidence and duration that could yield this phenomenon is of tremendous interest to researchers trying to understand the natural history of the disease and to develop efficient screening strategies. In this article, the authors present estimates of the age-specific asymptomatic incidence and average preclinical duration of prostate cancer. The methodological approach is to first estimate the age-specific incidence of new (stage AI) prostate cancers using preclinical prevalence data from autopsy studies performed between 1941 and 1964 and clinical incidence data for the years 1960-1986 from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. Then, the preclinical prevalence estimates are divided by the derived preclinical incidence estimates to yield estimates of the average duration of asymptomatic disease. The estimated mean duration among white men is between 11 and 12 years and appears to be approximately 1 year shorter for blacks than for whites. Comparison of the lifetime risks of preclinical and clinical disease suggests that approximately 75% of prostate cancers will never become diagnosed if clinical incidence remains at levels observed in 1984-1986, prior to the introduction of prostate-specific antigen (PSA) screening in the population.

Adult↗

Estimating asymptomatic duration in cancer: the AIDS connection.

Many chronic diseases, including AIDS and cancer, do not manifest themselves clinically until some time after their inception. In studies of disease natural history, the duration of the asymptomatic period is of interest-in AIDS, to predict the epidemic's course, and in cancer, to develop efficient screening strategies. This article provides a bridge between the two fields with respect to estimation of the asymptomatic period. By adapting AIDS methodology to cancer, the article identifies a non-parametric method for estimating the duration of the asymptomatic period in cancer. The method is similar to one developed by Louis et al. (Mathematical Biosciences, 40, 111-144 (1978)), and is designed to apply to data from a cohort of individuals, screened periodically. After reviewing the similarities and differences between the AIDS and cancer contexts, we develop an EM algorithm that, at convergence, yields a maximum or saddle point of the likelihood. We investigate the performance of the algorithm by means of a simulation study, explore the effect of adding a smoothing step to the estimation procedure, and adapt the method for use with a data set in which disease prevalence is low. We apply the method to data from the HIP breast cancer screening trial.

Acquired Immunodeficiency Syndrome↗

Use of a stochastic simulation model to identify an efficient protocol for ovarian cancer screening.

The intervention protocol for an ovarian cancer screening trial should be efficient as well as effective, because it may become the standard of care if the trial demonstrates mortality reduction. To identify an efficient ovarian cancer screening protocol, the effectiveness and cost-effectiveness of selected single modality and multimodal screening strategies were estimated using a stochastic simulation model. Screening was simulated over a 30-year period in a hypothetical cohort of 1 million women aged 50 at the beginning of the period. The net present value of the cost per year of life saved was estimated for six protocols involving transvaginal sonography (TVS) and/or the tumor antigen CA 125. Internal and external validation was performed, and sensitivity analyses were conducted to assess the robustness of the ranking of the strategies. A multimodal strategy involving CA 125 with a threshold for positivity of either elevation above 35 U/ml or doubling since the previous screen, followed by TVS only if CA 125 is positive, was found to be efficient in the sense that no other strategies saved as many years of life at lower cost per year of life saved. Used annually, this strategy cost under $100,000 per year of life saved over a range of assumptions. The model's predictions are consistent with results reported in the literature regarding the performance of TVS and CA 125. The multimodal strategy used annually or every six months was efficient compared to either ultrasound or CA 125 used alone, over a range of assumptions. Simulation of screening may be useful in selecting a screening protocol to be tested in a randomized controlled trial.

Aged↗

Estimating medical costs from incomplete follow-up data.

Estimation of the average total cost for treating patients with a particular disease is often complicated by the fact that the survival times are censored on some study subjects and their subsequent costs are unknown. The naive sample average of the observed costs from all study subjects or from the uncensored cases only can be severely biased, and the standard survival analysis techniques are not applicable. To minimize the bias induced by censoring, we partition the entire time period of interest into a number of small intervals and estimate the average total cost either by the sum of the Kaplan-Meier estimator for the probability of dying in each interval multiplied by the sample mean of the total costs from the observed deaths in that interval or by the sum of the Kaplan-Meier estimator for the probability of being alive at the start of each interval multiplied by an appropriate estimator for the average cost over the interval conditional on surviving to the start of the interval. The resultant estimators are consistent if censoring occurs solely at the boundaries of the intervals. In addition, the estimators are asymptotically normal with easily estimated variances. Extensive numerical studies show that the asymptotic approximations are adequate for practical use and the biases of the proposed estimators are small even when censoring may occur in the interiors of the intervals. An ovarian cancer study is provided.

Aged↗

Age-specific prostate-specific antigen: a reassessment.

BACKGROUND: Our objective was to compare expected survival benefits when screening for prostate cancer with PSA, using an age-specific bound relative to a cutoff of 4.0 ng/ml. METHODS: We used a decision analysis modeling the cancer yield in a cohort screened by both screening tests, and the survival of cancer cases given screen detection and in the absence of screening. Expected cancer yields and positive predictive values were from an ultrasound-guided biopsy series. Stage distributions of screen-detected cases were obtained from the literature. For localized causes, survival given screen detection was assumed to be equal to normal life expectancy for the population. For these cases, survival in the absence of screening was modeled as time from clinical diagnosis to death added to time remaining after time of screen and before clinical diagnosis was made (lead time). For nonlocalized cases at screen detection, survival given screen detection was assumed to be equal to survival in the absence of screening. The average difference between expected survival with and without screening as calculated for age-specific PSA and for PSA > 4.0 ng/ml and compared. RESULTS: Average years of life saved per subject screened using PSA > 4.0 ng/ml were comparable to those using the age-specific bound. Average years of life saved per cancer case, however, appeared to be potentially greater for PSA > 4.0 ng/ml than for age-specific. PSA. PSA > 4.0 ng/ml detected markedly more prostate cancer cases than age-specific PSA. CONCLUSIONS: Using a bound of 4.0 ng/ml for all ages appears to be more efficient in identifying men with cancer in a screening cohort, which translates into a greater expected survival benefit per cancer case.

Aged↗

Estimating the costs attributable to a disease with application to ovarian cancer.

This article is concerned with the methodological issues that arise when estimating the expected costs attributable to a disease. In particular, the article considers methods appropriate for handling incomplete or censored cost and survival data, incorporating discounting, and computing attributable costs. After motivating the need for an estimate of the average, present value of the attributable costs, we present the Kaplan-Meier sample-average (KMSA) estimator, which takes into account the censored nature of the data that are typically available. We investigate the statistical properties of the estimator and compare it to others employed in the literature, showing how certain methods for incorporating discounting can introduce bias. We demonstrate the utility of the estimator by applying it to estimation of the costs attributable to ovarian cancer, using data from a database linking Medicare claims with the Surveillance, Epidemiology, and End Results cancer registry. Our analysis suggests that the average, present value of the 15-year costs attributable to ovarian cancer is $21,285 for local-stage cases and $32,126 for distant-state cases in 1990 dollars.

Aged↗

Serum prostate-specific antigen and digital rectal examination for early detection of prostate cancer in a national community-based program. The Prostate Cancer Education Council.

OBJECTIVES: This study analyzed methods of prostate cancer early detection in community settings throughout the United States against standards and findings of earlier studies conducted at academic medical centers. METHODS: The study was conducted at 148 clinical centers during Prostate Cancer Awareness Week in September 1993 and continued through June 1994. A total of 31,953 eligible subjects were tested by both digital rectal examination (DRE) and prostate-specific antigen (PSA). PSA was tested with the Abbott IMx PSA assay and reported by Roche Biomedical, Inc. RESULTS: The study confirmed that elevated PSA levels (greater than 4.0 ng/mL) aid in the detection of organ-confined prostate cancer when used in conjunction with the DRE. Reflecting more conservative biopsy decision-making practices, study results nonetheless are comparable to earlier reports. Among 1307 subjects who underwent biopsy, 322 cancers were detected. The cancer detection rate was 3.6% for PSA, 3.0% for DRE, and 4.7% if either test result was positive. The positive predictive value (PPV) for elevated PSA levels (greater than 4.0 ng/mL) was 3l.6%, significantly better (P < 0.0001) than the PPV for abnormal DRE results (25.5%). Nearly 90% (88.9%) of staged cancers were diagnosed as localized. Elevated PSA levels detected more localized cancers (76 of 105 [72.4%]) than the DRE (72 of 105 [68.6%]). Of localized tumors, 33 (31.4%) were missed by DRE and detected solely by PSA, and 29 (27.6%) were missed by PSA and detected solely by DRE. The combined use of the two methods detected 33 additional localized tumors. CONCLUSIONS: Community practice throughout the United States demonstrates that PSA and DRE are consistently effective and efficient in the early detection of prostate cancer.

Aged↗