Michael H. Dong MPH, DrPA, PhD  readings Epidemiology and Risk Assessment (4th of 10 Lectures on Toxicologic Epidemiology)

Taken in the early ’90s, when desktop computers were still a luxury.

Learning Objectives Appreciate the recent advances in epidemiology pertinent to health risk assessment (RA). Study the epidemiologic approaches to human exposure assessment. Learn about the biomarkers used in epidemiology as well as in RA.

Performance Objectives Able to list and describe the recent advances in epidemiology pertinent to health risk assessment (RA). To describe the epidemiologic approaches to exposure assessment. To discuss the strengths and limitations of the use of biomarkers in epidemiology and in RA.

Health Statutes & Regulations Toxicity Studies/Data Research Developments

Recent Advances in Epidemiology Branching out from general epidemiology. Specialty disciplines now including: psychosocial; pharmaco-; occupational; environmental; nutritional; genetic; molecular; cancer epidemiology; and more.

Psychosocial Epidemiologysocial Epidemiology Determinants of disease: social; psychological; behavioral factors. Not directly of regulatory concern. But offering valuable information for health risk assessment.

Pharmacoepidemiology Studying the use, efficacy, and safety of pharmaceuticals. Beginning to flourish in 1980s. Adding a new twist to the regular course of health risk assessment.

Nutritional Epidemiology Studying the role of nutrition/ diet in the etiology of disease. Nutritional epidemiologists conducted the first clinical trials. Human and social factors affect dietary intake.

GeneticGenetic and Molecular EpidemiologyMolecular Actually two separate branches. Molecular: studying with known genes. Genetic: studying with unknown genes. Useful in flagging preclinical effects of exposure.

Cancer Epidemiology Related closely to molecular and genetic epidemiology. Now more into identifying and quantifying nutritional and other environmental carcinogens. Epidemiology on cancer effects becoming more available for health risk assessment.

EnvironmentalEnvironmental & Occu- pational Epidemiology Actually two separate branches. But both are linked together due to studying exposures to common toxic agents which are relatively more preventable. Occupational epidemiology tends to use biomarkers more.

Clinical Trials Were conducted as early as Sometimes referred to as human intervention trials. Used to test not only treatment but also adverse (side) effects. A simplified or special version of health risk assessment.

Phases of Regulatory Clinical Trials Preclinical: a series of laboratory or animal studies. Trial Phases: (I) testing for human safety; (II) testing for efficacy; (III) overall trial assessment. Postlicensing surveillance. Ideally should follow a double- blind randomization design.

Meta-Analysis of Clinical Trial Data First used around Uses routine statistical methods on data pooled from various trials typically not following the same study protocol. A controversial technique unacceptable to some statisticians.

Basic Epidemiologic Study Designs Using primarily observational data. Descriptive studies. Cohort studies. Case-control studies. Cross-sectional studies. Ecological studies.

Guidance for Epidemiology Studies Epidemiologic study designs can be used to assess human exposures. Good epidemiology practices by: International Society for Pharmaco- epidemiology; International Epidemiological Association; and World Health Organization. International Society for Pharmaco- epidemiologyInternational Epidemiological Association World Health Organization

Human Exposure: Basic Definition Human exposure to a toxic agent is defined as the (level of) contact of a person with the toxicant. Human exposures can be categorized by route of entry; exposure source; and exposure duration.

Human Exposure: Methods and Advances Methods: direct monitoring of individuals; and from measurement of environmental levels. Advances: Social Readjustment Rating Scale; Stress Process Model; geographic information system; biomarkers, etc.

Use of Biomarkers Limitations: low detection levels; compliance with sample collection. Related to biological monitoring. Types of biomarkers: for exposure; adverse response; susceptibility. Best estimate for aggregate dose.

Criteria of Selection of Biomarkers Criteria: availability; specificity; invasiveness; persistence; time-to- appearance; intra- and interperson variability. Multiple factors causing biological variation in dose-response.

Biomarkers: Legal and Ethical Considerations Legal authority as barrier; privacy act. Ethical implications concerning the subject’s right-to-know. These considerations making biomarkers useful at a slow pace.

Overview of Next Lecture Toxicologic Side of Epidemiology Illustrating this side through use of historical cases. Epidemiologic activities might have initiated/dominated in these cases. But the toxicologic side was also there and critical.