Epidemiological Methods: About Time

Epidemiological studies often produce false positive results due to use of statistical approaches that either ignore or distort time. The three time-related issues of focus in this discussion are: (1) cross-sectional vs. cohort studies, (2) statistical significance vs. public health significance, and (3), how risk factors “work together” to impact public health significance. The issue of time should be central to all thinking in epidemiology research, affecting sampling, measurement, design, analysis and, perhaps most important, the interpretation of results that might influence clinical and public-health decision-making and subsequent clinical research

Moderators, Mediators, and Other Predictors of Risperidone Response in Children with Autistic Disorder and Irritability

Objective/Background: The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure in an 8-week double-blind, placebo-controlled trial for irritabilityin autistic disorder. This paper explores moderators and mediators of this effect. Method: Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the evaluation of the results. Results: Only baseline severity moderated treatment response: Higher severity showed greater improvement for risperidone but not for placebo. Weight gain mediated treatment response negatively: Those who gained more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity negatively predicted outcome. Risperidone moderated the effect of change in 5'-nucleotidase, a marker of zinc status, for which decrease was associated with improvement only with risperidone, not with placebo. Conclusion: The benefit–risk ratio of risperidone is better with greater symptom severity. Risperidone can be individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and absence of co-morbid problems non-specifically predict better outcome. Mineral interactions with risperidone deserve further study

Statistics and Policy Decisions: Issues in Statistical Analyses

When national policy decisions are to be guided by the results of statistical analyses, it is important, to avoid being misled to look beyond the authors' conclusions and first to assess the study design, measurement and analytic methods, in order to decide whether a study's conclusions rest on a solid foundation. In particular, observational studies must be carefully and critically evaluated. Using a study widely cited concerning the effects of low-level lead exposure and IQ, we illustrate several methodological errors, long known but often ignored. The goal is not to settle the controversies about the effect of lead on IQ, nor to disparage observational studies, for they are the foundation of all studies done to guide policy, but to encourage additional care in the use of such studies to address policy questions