Basic Concepts In Epidemiology

1. Basic Concepts In Epidemiology Amit Khera, MD, MSc June 7, 2006

2. Epidemiology “the study of the distribution and determinants of disease frequency”

3. John Snow(1813-1858) Father of epidemiology London cholera epidemic of 1854 Broad Street Pump Anesthesiologist– wrote on the use of ether in 1847 Thought cholera was transmitted by polluted water rather than through vapors Previously, had showed that cholera more prevalent in those using one company than the other– water from lower Thames which was contaminated by sewage 1854- 500 people died in 10 days. Examined 5 water pumps and found that those who had cholera were more likely to use one pump on Broad Street– handle removed Anesthesiologist– wrote on the use of ether in 1847 Thought cholera was transmitted by polluted water rather than through vapors Previously, had showed that cholera more prevalent in those using one company than the other– water from lower Thames which was contaminated by sewage 1854- 500 people died in 10 days. Examined 5 water pumps and found that those who had cholera were more likely to use one pump on Broad Street– handle removed

4. Epidemiology EXPOSURES determinants of disease (association) OUTCOMES endpoints of a study (disease) Sometimes outcomes alone are of interest (descriptive stats) Sometimes, want to link to an exposure distribution- descriptive characteristics about an outcome outcome can be anything– must define earlySometimes outcomes alone are of interest (descriptive stats) Sometimes, want to link to an exposure distribution- descriptive characteristics about an outcome outcome can be anything– must define early

5. Outcome Measures Prevalence proportion- proportion of a population with the outcome (disease) at a single point in “time” Incidence- the number or proportion of individuals developing the outcome (disease) during a period of time incidence proportion (risk) incidence rate Prevalence- time can be calendar date, age (21yo with...), life event (at retirement) Prevalence measures disease status, not disease onset Incidence proportion- 20% incidence of panic attacks in UTSW medical students in their first year rate- 100 person-years? can be 10 people for 10 years or 100 people for 1 year Prevalence- time can be calendar date, age (21yo with...), life event (at retirement) Prevalence measures disease status, not disease onset Incidence proportion- 20% incidence of panic attacks in UTSW medical students in their first year rate- 100 person-years? can be 10 people for 10 years or 100 people for 1 year

7. Lipid Levels and Heart Disease Low HDL-C Levels Increase CHD Risk Even When Total-C Is Normal (Framingham) Low high-density lipoprotein cholesterol (HDL-C) levels (< 40 mg/dL) are associated with an increased risk of coronary heart disease (CHD) even if the total cholesterol (Total-C) level is < 200 mg/dL. This slide shows the CHD incidence over 14 years among Framingham Study subjects who were aged 48–83 years at baseline. Among those with HDL-C levels < 40 mg/dL and Total-C < 200 mg/dL, 11.24% experienced a CHD event. This incidence was virtually the same as that (11.91%) for subjects with HDL-C levels between 40–49 mg/dL and Total-C ? 260 mg/dL. References: Castelli WP, Garrison RJ, Wilson PW, et al. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA. 1986;256:2835–2838. Low HDL-C Levels Increase CHD Risk Even When Total-C Is Normal (Framingham) Low high-density lipoprotein cholesterol (HDL-C) levels (< 40 mg/dL) are associated with an increased risk of coronary heart disease (CHD) even if the total cholesterol (Total-C) level is < 200 mg/dL. This slide shows the CHD incidence over 14 years among Framingham Study subjects who were aged 48–83 years at baseline. Among those with HDL-C levels < 40 mg/dL and Total-C < 200 mg/dL, 11.24% experienced a CHD event. This incidence was virtually the same as that (11.91%) for subjects with HDL-C levels between 40–49 mg/dL and Total-C ? 260 mg/dL. References: Castelli WP, Garrison RJ, Wilson PW, et al. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA. 1986;256:2835–2838.

8. Linking Exposures to Outcomes Outcome measures are descriptive characteristics about distribution of the outcome ex: what is the prevalence of lung cancer? Measures of Association quantifying relationships Exposure can be anything- cigarettes, cholesterol, race, maternal age (not just biology) Ex- is smoking related to lung cancer? Exposure can be anything- cigarettes, cholesterol, race, maternal age (not just biology) Ex- is smoking related to lung cancer?

9. Measures of Association Difference Measures Risk Difference (absolute risk reduction)= Incidence exposed - Incidence unexposed

10. Quantitative way to measure how the exposure (statins) are related to the outcome (adverse CV events)– can quantify this relationship.Quantitative way to measure how the exposure (statins) are related to the outcome (adverse CV events)– can quantify this relationship.

11. Measures of Association Ratio Measures Risk Ratio Incidence Rate Ratio Hazard Ratio Odds Ratio Incidence exposed/Incidence unexposed

12. Odds ratio- odds of death in treatment group/odds of death in control groupOdds ratio- odds of death in treatment group/odds of death in control group

13. Are There Alternative Explanations? Measures of Validity Internal Validity Chance- (p-value) Bias Confounding External Validity Generalizability Are there alternative explanations to your results?Are there alternative explanations to your results?

14. Bias Bias- systematic error affecting the results of the study Selection bias- association between disease and exposure occurs because of the way participants were selected, not by underlying truth Recall bias- occurrence of outcome results in increased recall of exposures ex: maternal recall bias Informational bias- differential misclassification of exposure or outcome (MD Behavior Bias) Meternal recall bias- mothers that have children with birth defects are more likely to remember what drugs/herbals they took– the event itself caused them to remember more clearly. May think that birth defects are associated with herbals.Meternal recall bias- mothers that have children with birth defects are more likely to remember what drugs/herbals they took– the event itself caused them to remember more clearly. May think that birth defects are associated with herbals.

15. Selection Bias STUDY A Patients in a CHF clinic were approached to be involved in the study 52% were found to have depression STUDY B Patients were randomly selected from a population-based study of CHF 23% were found to have depression In study A, patients who had depressive symptoms were more often approached to be in the study. They were selected because they were thought to have the outcome.In study A, patients who had depressive symptoms were more often approached to be in the study. They were selected because they were thought to have the outcome.

16. Confounding Outcome is Down’s Syndrome? what is exposure? Can do stratified analysis Ex: Gray hair and CAD; age is a confounder of the relationship between gray hair and CADOutcome is Down’s Syndrome? what is exposure? Can do stratified analysis Ex: Gray hair and CAD; age is a confounder of the relationship between gray hair and CAD

17. External Validity Generalizability- how well do these results apply to other populations? Ex: Framingham Heart Study Chinese Multi-provincial Cohort StudyChinese Multi-provincial Cohort Study

18. Study Types Observational cohort (follow-up) case-control cross-sectional (prevalence) Experimental randomized trial

19. Cohort Study Cohort study- study that follows or traces any designated group over a period of time Example– power lines and development of cancerExample– power lines and development of cancer

20. Exposure is prenatal cocaine useExposure is prenatal cocaine use

21. Case-Control Study

22. HMG-CoA Reductase Inhibitors and the Risk of Hip Fractures in Elderly PatientsJAMA 2004;283:3211-3216 Can introduce bias if select controls or cases based on their known exposures (ie: select controls because they are on a statin)Can introduce bias if select controls or cases based on their known exposures (ie: select controls because they are on a statin)

23. Cross-sectional Study

24. Randomized Controlled Trial Type of cohort study in which the exposures are assigned Gold standard for epidemiologic trials Randomization ensures equal distribution of confounders

27. Suggested Reading Rothman K.J. Epidemiology: An Introduction, New York: Oxford University Press, 2002. Hennekens CH, Buring JE. Epidemiology in Medicine, Boston: Little, Brown and Co., 1987