Accounting for rate instability and spatial patterns in the boundary analysis of cancer mortality maps.

Boundary analysis of cancer maps may highlight areas where causative exposures change through geographic space, the presence of local populations with distinct cancer incidences, or the impact of different cancer control methods. Too often, such analysis ignores the spatial pattern of incidence or mortality rates and overlooks the fact that rates computed from sparsely populated geographic entities can be very unreliable. This paper proposes a new methodology that accounts for the uncertainty and spatial correlation of rate data in the detection of significant edges between adjacent entities or polygons. Poisson kriging is first used to estimate the risk value and the associated standard error within each polygon, accounting for the population size and the risk semivariogram computed from raw rates. The boundary statistic is then defined as half the absolute difference between kriged risks. Its reference distribution, under the null hypothesis of no boundary, is derived through the generation of multiple realizations of the spatial distribution of cancer risk values. This paper presents three types of neutral models generated using methods of increasing complexity: the common random shuffle of estimated risk values, a spatial re-ordering of these risks, or p-field simulation that accounts for the population size within each polygon. The approach is illustrated using age-adjusted pancreatic cancer mortality rates for white females in 295 US counties of the Northeast (1970-1994). Simulation studies demonstrate that Poisson kriging yields more accurate estimates of the cancer risk and how its value changes between polygons (i.e. boundary statistic), relatively to the use of raw rates or local empirical Bayes smoother. When used in conjunction with spatial neutral models generated by p-field simulation, the boundary analysis based on Poisson kriging estimates minimizes the proportion of type I errors (i.e. edges wrongly declared significant) while the frequency of these errors is predicted well by the p-value of the statistical test.