The analysis of incomplete data using stochastic covariates

In the development of many diseases there are often associated random variables which continuously reflect the progress of a subject towards the final expression of the disease (failure). At any given time these processes, which we call stochastic covariates, may provide information about the current hazard and the remaining time to failure. Likewise, in situations when the specific times of key prior events are not known, such as the time of onset of an occult tumour or the time of infection with HIV-1, it may be possible to identify a stochastic covariate which reveals, indirectly, when the event of interest occurred. The analysis of carcinogenicity trials which involve occult tumours is usually based on the time of death or sacrifice and an indicator of tumour presence for each animal in the experiment. However, the size of an occult tumour observed at the endpoint represents data concerning tumour development which may convey additional information concerning both the tumour incidence rate and the rate of death to which tumour-bearing animals are subject. We develop a stochastic model for tumour growth and suggest different ways in which the effect of this growth on the hazard of failure might be modelled. Using a combined model for tumour growth and additive competing risks of death, we show that if this tumour size information is used, assumptions concerning tumour lethality, the context of observation or multiple sacrifice times are no longer necessary in order to estimate the tumour incidence rate. Parametric estimation based on the method of maximum likelihood is outlined and is applied to simulated data from the combined model. The results of this limited study confirm that use of the stochastic covariate tumour size results in more precise estimation of the incidence rate for occult tumours.     

A SCALE IN SEARCH OF A CONSTRUCT: COMMENTS ON GAVIN AND WAMBOLDT

The article examines some issues raised in Gavin and Wamboldt's (1992) recent study on the Family-of-Origin Scale (FOS) (Hovestadt, Anderson, Piercy, Cochran, & Fine, 1985). The discussion centers on unresolved concerns regarding the validity and utility of the FOS and on unsubstantiated and potentially misleading claims made in the Gavin and Wamboldt article. A case is made for conceptual and methodological precision in the study of family phenomena.     

Modelling data from single-photon emission computerized tomography

The completely random character of radioactive disintegration provides the basis of a strong justification for a Poisson linear model for single-photon emission computed tomography data, which can be used to produce reconstructions of isotope densities, whether by maximum likelihood or Bayesian methods. However, such a model requires the construction of a matrix of weights, which represent the mean rates of arrival at each detector of photons originating from each point within the body space. Two methods of constructing these weights are discussed, and reconstructions resulting from phantom and real data are presented.     

MEANINGFUL REGRESSION AND ASSOCIATION MODELS FOR CLUSTERED ORDINAL DATA

Many proposed methods for analyzing clustered ordinal data focus on the regression model and consider the association structure within a cluster as a nuisance. However, the association structure is often of equal interest—for example, temporal association in longitudinal studies and association between responses to similar questions in a survey. We discuss the use, appropriateness, and interpretability of various latent variable and Markov models for the association structure and propose a new structure that exploits the ordinality of the response. The models are illustrated with a study concerning opinions regarding government spending and an analysis of stability and change in teenage marijuana use over time, where we reveal different behavioral patterns for boys and girls through a comprehensive investigation of individual response profiles.     

Physiologically Based Liver Modeling and Risk Assessment

Because of the inherent complexity of biological systems, there is often a choice between a number of apparently equally applicable physiologically based models to describe uptake and metabolism processes in toxicology or risk assessment. These models may fit the particular data sets of interest equally well, but may give quite different parameter estimates or predictions under different (extrapolated) conditions. Such competing models can be discriminated by a number of methods, including potential refutation by means of strategic experiments, and their ability to suitably incorporate all relevant physiological processes. For illustration, three currently used models for steady-state hepatic elimination--the venous equilibration model, the parallel tube model, and the distributed sinusoidal perfusion model--are reviewed and compared with particular reference to their application in the area of risk assessment. The ability of each of the models to describe and incorporate such physiological processes as protein binding, precursor-metabolite relations and hepatic zones of elimination, capillary recruitment, capillary heterogeneity, and intrahepatic shunting is discussed. Differences between the models in hepatic parameter estimation, extrapolation to different conditions, and interspecies scaling are discussed, and criteria for choosing one model over the others are presented. In this case, the distributed model provides the most general framework for describing physiological processes taking place in the liver, and has so far not been experimentally refuted, as have the other two models. These simpler models may, however, provide useful bounds on parameter estimates and on extrapolations and risk assessments.