Estimating Sensitivity and Sojourn Time in Screening for Colorectal Cancer A Comparison of Statistical Approaches
TL;DR: Various analytic strategies for fitting exponential models to data from a screening program for colorectal cancer conducted in Calvados, France, between 1991 and 1994 are considered, yielding estimates of mean sojourn time and sensitivity.
Abstract: The effectiveness of cancer screening depends crucially on two elements: the sojourn time (that is, the duration of the preclinical screen-detectable period) and the sensitivity of the screening test. Previous literature on methods of estimating mean sojourn time and sensitivity has largely concentrated on breast cancer screening. Screening for colorectal cancer has been shown to be effective in randomized trials, but there is little literature on the estimation of sojourn time and sensitivity. It would be interesting to demonstrate whether methods commonly used in breast cancer screening could be used in colorectal cancer screening. In this paper, the authors consider various analytic strategies for fitting exponential models to data from a screening program for colorectal cancer conducted in Calvados, France, between 1991 and 1994. The models yielded estimates of mean sojourn time of approximately 2 years for 45- to 54-year-olds, 3 years for 55- to 64-year-olds, and 6 years for 65- to 74-year-olds. Estimates of sensitivity were approximately 75%, 50%, and 40% for persons aged 45-54, 55-64, and 65-74 years, respectively. There is room for improvement in all models in terms of goodness of fit, particularly for the first year after screening, but results from randomized trials indicate that the sensitivity estimates are roughly correct. Am J Epidemiol 1998;148:609-19.
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TL;DR: The approach is sensitive to relaxing the assumptions regarding the expected breast cancer incidence without screening and constant STS over time, and the results of long MST and low screen test sensitivity were confirmed with the new approach.
Abstract: ObjectivesMean sojourn time (MST) and screening test sensitivity (STS), is usually estimated by Markov models using incidence data from the first screening round and the interval between screening examinations. However, several screening programmes do not have full registration of cancers submerging after screening, and increased use of opportunistic screening over time can raise questions regarding the quality of interval cancer registration.Methods/settingsBased on the earlier used Markov model, formulas for expected number of cases given time since former screening activity was developed. Using questionnaire data for 336,533 women in the Norwegian Breast Cancer Screening Programme (NBCSP), mean square regression estimates of MST and STS were calculated.ResultsIn contrast to the previously used method, the new approach gave satisfactory model fit. MST was estimated to 5.6 years for women aged 50–59 years, and 6.9 years for women aged 60–69 years, and STS was estimated to 55% and 60%, respectively. Attem...
27 citations
09 Aug 2003
TL;DR: CMS has decided to provide for annual coverage of the screening iFOBT as an alternative to (or substitute for) the screening guaiac fecal-occult blood test (gFOBT), for all beneficiaries age 50 and older.
Abstract: Background Colorectal cancer screening is now recommended in the general population beginning at age 50 for those at average risk The most common colorectal cancer screening test in use in the United States is the guaiac based fecal occult blood test (FOBT) Colorectal cancer screening is now covered by Medicare with a reimbursement level of $450 for the guaiac test Immunochemical fecal occult blood tests (IFOBT) have tended to be more expensive and have not yet been widely used in the US In order to inform coverage and payment decisions related to the use of these tests, this report estimates the cost effectiveness of an immunochemical test with test performance parameters that are equivalent to or better than those associated with the guaiac test We also report the threshold payment level of the immunochemical test relative to the guaiac test, the level of payment for the immunochemical test that would result in cost-effectiveness equivalent to that of the comparative guaiac test Methods We use a micro-simulation model, MISCAN-COLON, developed and validated by Erasmus University to describe the natural history of the adenoma carcinoma sequence and the impact of screening on reducing colorectal cancer incidence and mortality The cost effectiveness of life years gained relative to costs for screening are derived for screening tests with different test performance characteristics We review the literature for guaiac and immunochemical tests to establish reasonable test performance levels of sensitivity and specificity for these tests Although the efficacy of FOBT screening was established using the guaiac based Hemoccult II test, the guaiac based Hemoccult SENSA test has higher sensitivity but lower specificity than Hemoccult II and recently has increased in use Consequently we consider both Hemoccult II and Hemoccult SENSA as base cases We assume base case values for Hemoccult II of 40% sensitivity for colorectal cancer, 10% sensitivity for adenomas ≥10 cm, 5% sensitivity for adenomas Results The cost effectiveness of the Hemoccult II FOBT ($1,071 per life year gained) is a very favorable level of cost-effectiveness in comparison to other cancer screening modalities Immunochemical tests, even with costs per test of $28 per test, still have a cost effectiveness ratio of no more than $4,500 per life year saved At a paymemt level of $28 for IFOBT and $450 for Hemoccult II, the incremental cost effectiveness ratio (ICER) for IFOBT is $11,000 per additional life-year saved assuming a specificity of 98% for IFOBT and $21,000 per additional life-year saved assuming a specificity of 95% for IFOBT The threshold payment level of the IFOBT, with 98% specificity for most test parameters considered, was in the range of $700 to $1300, which is only somewhat higher than the $450 of the base case Hemoccult II However when the IFOBT has specificity of 95%, then the threshold values for most test parameters considered were less than zero dollars Results for IFOBT are much more favorable if Hemoccult SENSA is assumed to be the base case and especially if IFOBT is assumed to operate at the more favorable specificity value of 98% A threshold payment level of $28 for IFOBT is exceeded if either or both of the following conditions are met: a) IFOBT is assumed to have the lower specificity value of 95% but much better values of sensitivity for the detection of adenomas than Hemoccult SENSA, or b) IFOBT is assumed to have sensitivity values equal to Hemoccult SENSA but the higher specificity value of 98% If we assume payment rates of $18 and $27 for IFOBT, then the corresponding threshold payment levels are $10 and $17 for Hemoccult II when IFOBT has 98% specificity and $5 and $14 for Hemoccult SENSA when assuming 95% specificity for IFOBT Conclusion Fecal occult blood tests, either guaiac based or immunochemical based, provide for a very cost effective intervention for reducing colorectal cancer incidence and mortality If the immunochemical fecal occult blood test maintains the high specificity of Hemoccult II (98%) and increases sensitivity for colorectal cancer to 70% over that of Hemoccult II (40%), then a unit cost level of approximately $1300 would provide a comparable cost-effectiveness to Hemoccult II at $450 per unit cost If the specificity of the immunochemical fecal occult blood test is assumed to be 95% when the sensitivity for colorectal cancer increases to 70%, then the threshold payment level for IFOBT would actually be lower than the current $450 However, further threshold analysis using Hemoccult SENSA as the base case with a sensitivity of 70% for colorectal cancer and specificity of 925% indicates that the immunochemical test could achieve a threshold payment level in excess of $28 when the more favorable assumptions about IFOBT are made Evidence about the relative specificity and sensitivity of IFOBT in comparison to Hemoccult II and Hemoccult SENSA is sparse and highly uncertain Therefore the scenarios under which the threshold payment level of $28 is exceeded for IFOBT, although potential possible, cannot be considered to be strongly evidence based If payment level of $18 and $27 are assumed for IFOBT, corresponding threshold payment levels for Hemoccult II would be higher than current payment levels while this would be true for Hemoccult SENSA only if the lower specificity value of 95% is assumed for IFOBT
25 citations
TL;DR: Applying the proposed formulas for estimating tumour progression and STS using a continuous tumour growth model to Norwegian data, the new approach gives similar results to previously published results based on interval data, confirming the earlier estimated large variation in tumours growth rates.
Abstract: As mammography screening aims to improve the prognosis through earlier detection/treatment, tumour progression and screening test sensitivity (STS) represent key parameters in the evaluation of screening programs. We will here study some methods for estimation of tumour progression and STS, and show how previously used methods can be combined and developed to utilise more of the data available in modern screening programs. Weedon-Fekjaer et al. recently suggested a study design using interview data about time since previous screening to estimate tumour progression and STS in a stepwise Markov model. While useful, the approach does not utilise tumour size measurements, nor link tumour progression to tumour size. Hence, we will here propose formulas for estimating tumour progression and STS using a continuous tumour growth model. To estimate tumour progression and STS, tumour growth curves are followed from one screening to the next, and probabilities for all combinations of tumour sizes at repeated screenin...
25 citations
TL;DR: The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat rounds need to be recognised for an optimal regimen of screening.
Abstract: Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan–Meier (K-M) survival rates, separately for baseline and annual rounds. Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long-term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81–89%) for adenocarcinoma, 74% (95% CI 63–85%) for squamous cell, 48% (95% CI 34–62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. • Lung cancer aggressiveness varies considerably by cell type and nodule consistency.
• Kaplan–Meier survival rates varied by cell type between 100% and 48%.
• The percentages of lung cancers by cell type in screening rounds reflect screening biases.
• Rank ordering by cell type survival is consistent with that by lead times.
• Empirical evidence provides critical information for the regimen of screening.
25 citations
TL;DR: IEEs, which can enhance theoscopic findings of the colon lesions, have the poential to improve the detection and differentiation of olon neoplasms.
25 citations
References
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TL;DR: The focus is on applied inference for Bayesian posterior distributions in real problems, which often tend toward normal- ity after transformations and marginalization, and the results are derived as normal-theory approximations to exact Bayesian inference, conditional on the observed simulations.
Abstract: The Gibbs sampler, the algorithm of Metropolis and similar iterative simulation methods are potentially very helpful for summarizing multivariate distributions. Used naively, however, iterative simulation can give misleading answers. Our methods are simple and generally applicable to the output of any iterative simulation; they are designed for researchers primarily interested in the science underlying the data and models they are analyzing, rather than for researchers interested in the probability theory underlying the iterative simulations themselves. Our recommended strategy is to use several independent sequences, with starting points sampled from an overdispersed distribution. At each step of the iterative simulation, we obtain, for each univariate estimand of interest, a distributional estimate and an estimate of how much sharper the distributional estimate might become if the simulations were continued indefinitely. Because our focus is on applied inference for Bayesian posterior distributions in real problems, which often tend toward normality after transformations and marginalization, we derive our results as normal-theory approximations to exact Bayesian inference, conditional on the observed simulations. The methods are illustrated on a random-effects mixture model applied to experimental measurements of reaction times of normal and schizophrenic patients.
13,884 citations
TL;DR: In this paper, three sampling-based approaches, namely stochastic substitution, the Gibbs sampler, and the sampling-importance-resampling algorithm, are compared and contrasted in relation to various joint probability structures frequently encountered in applications.
Abstract: Stochastic substitution, the Gibbs sampler, and the sampling-importance-resampling algorithm can be viewed as three alternative sampling- (or Monte Carlo-) based approaches to the calculation of numerical estimates of marginal probability distributions. The three approaches will be reviewed, compared, and contrasted in relation to various joint probability structures frequently encountered in applications. In particular, the relevance of the approaches to calculating Bayesian posterior densities for a variety of structured models will be discussed and illustrated.
6,294 citations
Journal Article•
TL;DR: Stochastic substitution, the Gibbs sampler, and the sampling-importance-resampling algorithm can be viewed as three alternative sampling- (or Monte Carlo-) based approaches to the calculation of numerical estimates of marginal probability distributions.
Abstract: Stochastic substitution, the Gibbs sampler, and the sampling-importance-resampling algorithm can be viewed as three alternative sampling- (or Monte Carlo-) based approaches to the calculation of numerical estimates of marginal probability distributions. The three approaches will be reviewed, compared, and contrasted in relation to various joint probability structures frequently encountered in applications. In particular, the relevance of the approaches to calculating Bayesian posterior densities for a variety of structured models will be discussed and illustrated.
6,223 citations
Book•
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01 Jan 1996
TL;DR: Mathematica has defined the state of the art in technical computing for over a decade, and has become a standard in many of the world's leading companies and universities as discussed by the authors.
Abstract: From the Publisher:
Mathematica has defined the state of the art in technical computing for over a decade, and has become a standard in many of the world's leading companies and universities From simple calculator operations to large-scale programming and the preparation of interactive documents, Mathematica is the tool of choice
3,566 citations
[...]
01 Jan 1996
TL;DR: From the Publisher: Mathematica has defined the state of the art in technical computing for over a decade, and has become a standard in many of the world's leading companies and universities.
Abstract: From the Publisher:
Mathematica has defined the state of the art in technical computing for over a decade, and has become a standard in many of the world's leading companies and universities. From simple calculator operations to large-scale programming and the preparation of interactive documents, Mathematica is the tool of choice.
3,115 citations