title: Flexible regression models for rate differences, risk differences and relative risks.
abstract: Generalized additive models (GAMs) based on the binomial and Poisson distributions can be used to provide flexible semi-parametric modelling of binary and count outcomes. When used with the canonical link function, these GAMs provide semi-parametrically adjusted odds ratios and rate ratios. For adjustment of other effect measures, including rate differences, risk differences and relative risks, non-canonical link functions must be used together with a constrained parameter space. However, the algorithms used to fit these models typically rely on a form of the iteratively reweighted least squares algorithm, which can be numerically unstable when a constrained non-canonical model is used. We describe an application of a combinatorial EM algorithm to fit identity link Poisson, identity link binomial and log link binomial GAMs in order to estimate semi-parametrically adjusted rate differences, risk differences and relative risks. Using smooth regression functions based on B-splines, the method provides stable convergence to the maximum likelihood estimates, and it ensures that the estimates always remain within the parameter space. It is also straightforward to apply a monotonicity constraint to the smooth regression functions. We illustrate the method using data from a clinical trial in heart attack patients.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Donoghoe
authors.forename: Ian C
authors.initials: IC
authors.lastname: Marschner
mesh_terms: D006801:Humans; D015233:Models, Statistical; D009203:Myocardial Infarction / Q000453:epidemiology; D012044:Regression Analysis; D012306:Risk