Time-to-event estimation of birth prevalence trends: A method to enable investigating the etiology of childhood disorders including autism.

Abstract

An unbiased, widely accepted estimate of the rate of occurrence of new cases of autism over time would facilitate progress in understanding the causes of autism. The same may also apply to other disorders. While incidence is a widely used measure of occurrence, birth prevalence-the proportion of each birth year cohort with the disorder-is the appropriate measure for disorders and diseases of early childhood. Studies of autism epidemiology commonly speculate that estimates showing strong increases in rate of autism cases result from an increase in diagnosis rates rather than a true increase in cases. Unfortunately, current methods are not sufficient to provide a definitive resolution to this controversy. Prominent experts have written that it is virtually impossible to solve. This paper presents a novel method, time-to-event birth prevalence estimation (TTEPE), to provide accurate estimates of birth prevalence properly adjusted for changing diagnostic factors. It addresses the shortcomings of prior methods. TTEPE is based on well-known time-to-event (survival) analysis techniques. A discrete survival process models the rates of incident diagnoses by birth year and age. Diagnostic factors drive the probability of diagnosis as a function of the year of diagnosis. TTEPE models changes in diagnostic criteria, which can modify the effective birth prevalence when new criteria take effect. TTEPE incorporates the development of diagnosable symptoms with age. General-purpose optimization software estimates all parameters, forming a non-linear regression. The paper specifies all assumptions underlying the analysis and explores potential deviations from assumptions and optional additional analyses. A simulation study shows that TTEPE produces accurate parameter estimates, including trends in both birth prevalence and the probability of diagnosis in the presence of sampling effects from finite populations. TTEPE provides high power to resolve small differences in parameter values by utilizing all available data points.