Joint distribution of simultaneous exposures to several carcinogens in a case–control study: sample size determination

Abstract

Consider a population of individuals who are free of a disease under study, and who are exposed simultaneously at random exposure levels, say X,Y,Z,… to several risk factors which are suspected to cause the disease in the populationm. At any specified levels X=x, Y=y, Z=z, …, the incidence rate of the disease in the population ot risk is given by the exposure–response relationship r(x,y,z,…) = P(disease|x,y,z,…). The present paper examines the relationship between the joint distribution of the exposure variables X,Y,Z, … in the population at risk and the joint distribution of the exposure variables U,V,W,… among cases under the linear and the exponential risk models. It is proven that under the exponential risk model, these two joint distributions belong to the same family of multivariate probability distributions, possibly with different parameters values. For example, if the exposure variables in the population at risk have jointly a multivariate normal distribution, so do the exposure variables among cases; if the former variables have jointly a multinomial distribution, so do the latter. More generally, it is demonstrated that if the joint distribution of the exposure variables in the population at risk belongs to the exponential family of multivariate probability distributions, so does the joint distribution of exposure variables among cases. If the epidemiologist can specify the differnce among the mean exposure levels in the case and control groups which are considered to be clinically or etiologically important in the study, the results of the present paper may be used to make sample size determinations for the case–control study, corresponding to specified protection levels, i.e., size α and 1–β of a statistical test. The multivariate normal, the multinomial, the negative multinomial and Fisher's multivariate logarithmic series exposure distributions are used to illustrate our results.

Keywords:

• clinical or etiologic significance
• relative risk
• logistic model
• multivariate normal distribution