Cluster detection methods applied to the Upper Cape Cod cancer data

BACKGROUND: A variety of statistical methods have been suggested to assess the degree and/or the location of spatial clustering of disease cases. However, there is relatively little in the literature devoted to comparison and critique of different methods. Most of the available comparative studies rely on simulated data rather than real data sets. METHODS: We have chosen three methods currently used for examining spatial disease patterns: the M-statistic of Bonetti and Pagano; the Generalized Additive Model (GAM) method as applied by Webster; and Kulldorff's spatial scan statistic. We apply these statistics to analyze breast cancer data from the Upper Cape Cancer Incidence Study using three different latency assumptions. RESULTS: The three different latency assumptions produced three different spatial patterns of cases and controls. For 20 year latency, all three methods generally concur. However, for 15 year latency and no latency assumptions, the methods produce different results when testing for global clustering. CONCLUSION: The comparative analyses of real data sets by different statistical methods provides insight into directions for further research. We suggest a research program designed around examining real data sets to guide focused investigation of relevant features using simulated data, for the purpose of understanding how to interpret statistical methods applied to epidemiological data with a spatial component

Evaluation of the Performance of Smoothing Functions in Generalized Additive Models for Spatial Variation in Disease

Generalized additive models (GAMs) with bivariate smoothing functions have been applied to estimate spatial variation in risk for many types of cancers. Only a handful of studies have evaluated the performance of smoothing functions applied in GAMs with regard to different geographical areas of elevated risk and different risk levels. This study evaluates the ability of different smoothing functions to detect overall spatial variation of risk and elevated risk in diverse geographical areas at various risk levels using a simulation study. We created five scenarios with different true risk area shapes (circle, triangle, linear) in a square study region. We applied four different smoothing functions in the GAMs, including two types of thin plate regression splines (TPRS) and two versions of locally weighted scatterplot smoothing (loess). We tested the null hypothesis of constant risk and detected areas of elevated risk using analysis of deviance with permutation methods and assessed the performance of the smoothing methods based on the spatial detection rate, sensitivity, accuracy, precision, power, and false-positive rate. The results showed that all methods had a higher sensitivity and a consistently moderate-to-high accuracy rate when the true disease risk was higher. The models generally performed better in detecting elevated risk areas than detecting overall spatial variation. One of the loess methods had the highest precision in detecting overall spatial variation across scenarios and outperformed the other methods in detecting a linear elevated risk area. The TPRS methods outperformed loess in detecting elevated risk in two circular areas

A power comparison of generalized additive models and the spatial scan statistic in a case-control setting

<p>Abstract</p> <p>Background</p> <p>A common, important problem in spatial epidemiology is measuring and identifying variation in disease risk across a study region. In application of statistical methods, the problem has two parts. First, spatial variation in risk must be detected across the study region and, second, areas of increased or decreased risk must be correctly identified. The location of such areas may give clues to environmental sources of exposure and disease etiology. One statistical method applicable in spatial epidemiologic settings is a generalized additive model (GAM) which can be applied with a bivariate LOESS smoother to account for geographic location as a possible predictor of disease status. A natural hypothesis when applying this method is whether residential location of subjects is associated with the outcome, i.e. is the smoothing term necessary? Permutation tests are a reasonable hypothesis testing method and provide adequate power under a simple alternative hypothesis. These tests have yet to be compared to other spatial statistics.</p> <p>Results</p> <p>This research uses simulated point data generated under three alternative hypotheses to evaluate the properties of the permutation methods and compare them to the popular spatial scan statistic in a case-control setting. Case 1 was a single circular cluster centered in a circular study region. The spatial scan statistic had the highest power though the GAM method estimates did not fall far behind. Case 2 was a single point source located at the center of a circular cluster and Case 3 was a line source at the center of the horizontal axis of a square study region. Each had linearly decreasing logodds with distance from the point. The GAM methods outperformed the scan statistic in Cases 2 and 3. Comparing sensitivity, measured as the proportion of the exposure source correctly identified as high or low risk, the GAM methods outperformed the scan statistic in all three Cases.</p> <p>Conclusions</p> <p>The GAM permutation testing methods provide a regression-based alternative to the spatial scan statistic. Across all hypotheses examined in this research, the GAM methods had competing or greater power estimates and sensitivities exceeding that of the spatial scan statistic.</p

Spatial Epidemiology of Birth Defects in the United States and the State of Utah Using Geographic Information Systems and Spatial Statistics

Oral clefts are the most common form of birth defects in the United States (US) and the State of Utah has among the highest prevalence of oral clefts in the nation. The overall objective of this dissertation was to examine the spatial distribution of oral clefts and their linkage with a broad range of demographic, behavioral, social, economic, and environmental risk factors through the application of Geographic Information Systems (GIS) and spatial statistics. Using innovative linked micromaps plots, we investigated the geographic patterns of oral clefts occurrence from 1998 to 2002 and their relationships with maternal smoking rates and proportion of American Indians and Alaskan Natives (AIAN) at large scales across the US. The findings indicated higher oral clefts occurrence in the southwest and the midwest and lower occurrence in the east. Furthermore, these spatial patterns were significantly related to the smoking rates and AIAN. Then at the small area level, hierarchical Bayesian models were built to examine the spatial variation in oral clefts risk in the State of Utah from 1995 to 2004 and to assess association with mothers using tobacco, mothers consuming alcohol during pregnancy, and the proportion of mothers with no high school diploma. Next, multi-scalar spatial clustering and cluster techniques were used to test the hypothesis whether there was spatial clustering of oral clefts anywhere in the State of Utah and whether there were statistically significant local clusters with elevated oral cleft cases. Results generally revealed modest spatial variation in oral clefts risk in the State of Utah, with no pronounced spatial clustering, indicating environmental exposures are unlikely plausible cause of oral clefts. However, a few notable areas within Tri-County Local Health District, Provo/Brigham Young University, and North Orem had a tendency toward elevated oral clefts cases. Investigation of the maternal characteristics of these potential clusters supports the hypotheses that maternal smoking, lower education level, and family history are possible causes of oral clefts. Throughout this dissertation, we demonstrated how birth defects data collected by state and local surveillance systems coupled with GIS and spatial statistics methods can be useful in exploratory etiologic research of birth defects