Michael H. DongMPH, DrPA, PhD

readings

Epidemiology andRisk Assessment

(4th of 10 Lectures onToxicologic 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 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.

Genetic and Molecular Epidemiology

• 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.

Environmental & 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 1537.

• 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 1976.• 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.

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.