Additive isotonic regression models in epidemiology

Stone's method for assessing disease risk around a point source through iso tonic regression is routinely used in spatial epidemiology. It is useful in situations where the relationship of risk with exposure (distance being co mmonly used as a surrogate variable) is assumed monotonic but otherwise of unknown form. This paper extends this method to non-spatial epidemiology, w here typically two or more risk factors are present. The methodology descri bed is based on the additive isotonic model approach of Bacchetti; versions appropriate to count (Poisson) data and case-control (binomial) data are d escribed. In both cases, adjustment for covariates is incorporated, and a M onte Carlo method of hypothesis testing and interval estimation is presente d. The methodology is illustrated through a case-control example concerning the analysis of the possible effect of preconceptional external ionizing r adiation doses on the sex ratio at birth among children of fathers working at the Sellafield nuclear installation, Cumbria, U.K. Copyright (C) 2000 Jo hn Wiley & Sons, Ltd.