2. Session II Study Design

3. Session Overview Developing and testing hypotheses Study Designs: –Selection –Implementation Sampling

4. Learning Objectives Understand the differences in methodology between various study designs Be able to describe the advantages and disadvantages of alternative study designs Know how to assess which study design to apply during an outbreak investigation Understand how to select cases and controls in a case-control study design Understand sampling

5. Basic Steps of an Outbreak Investigation 1.Verify the diagnosis and confirm the outbreak 2.Define a case and conduct case finding 3.Tabulate and orient data: time, place, person 4.Take immediate control measures 5.Formulate and test hypothesis 6.Plan and execute additional studies 7.Implement and evaluate control measures 8.Communicate findings

6. Exposure and Outcome A study considers two main factors: exposure and outcome Exposure refers to factors that might influence one’s risk of disease –Smoking –Eating at a particular restaurant Outcome refers to case definitions –Individuals who do and do not have the disease/condition of interest

7. Developing Hypotheses A hypothesis is an educated guess about an association that is testable in a scientific investigation Descriptive data provide information to develop hypotheses Hypotheses tend to be broad initially and are then refined to have a narrower focus

8. Example Hypothesis: People who ate at the church picnic were more likely to become ill –Exposure is eating at the church picnic –Outcome is illness - diarrhea and fever, where diarrhea is defined as at least 3 soft stools in a 24 hour period Hypothesis: People who ate the egg salad at the church picnic were more likely to have laboratory- confirmed Salmonella –Exposure is eating egg salad at the church picnic –Outcome is laboratory confirmation of Salmonella

9. Analytic Studies Used to test the current hypothesis: –Is there an association between exposure and disease? –How strong is the association?

10. Analytic Studies Two types used in outbreak investigations –Cohort –Case-control

11. Definition of a Cohort In epidemiology, “Any designated group of individuals who are followed or traced over a period of time.” - Last, JM. A Dictionary of Epidemiology, 3 rd ed. New York: Oxford University Press, 1995

12. Cohort Study Types A cohort study analyzes an exposure / disease relationship within the entire cohort. Prospective –The Framingham Study Retrospective –Usually used in outbreak investigations

13. Cohort Studies DiseaseNo Disease Study Population Exposed Non-exposed No DiseaseDisease Exposure is self selected Follow through time

14. Cohort Study Identify cohort –Do not select cohort so that either everyone is exposed or everyone is diseased

15. Cohort Studies: Prospective vs. Retrospective ExposureOutcome ProspectiveAssessed at beginning of study Followed into the future for outcome RetrospectiveAssessed at some point in the past Outcome has already occurred

16. Cohort Study Preferred study design when: –Members of cohort are easily identifiable –Members of a cohort are easily accessible –Exposure is rare –There may be multiple diseases involved

17. Cohort Study Example Recent norovirus outbreaks on cruise ships Attempt to interview all passengers Collect food history information MMWR: December 13, 2002 / 51(49);1112-1115

18. Cohort Study Examples Shigellosis among swimmers in a Georgia park – Used park registry to identify park visitors Iwamoto M, Hlady G, Jeter M et al. Shigellosis among Swimmers in a Freshwater Lake-Georgia, 2003. Presented at the 53 rd Annual Epidemic Intelligence Service Conference. Atlanta, GA. April, 2004. Whirlpools and Methicillin-Resistant Staphylococcus aureus –Occurred on a college football team Begier EM, Barrett FK, Mshar PA et al. Body Shaving, Whirlpools, and Football: An Out break of Methicillin-Resistant Staphylococcus aureus Cutaneous Infections in a College Football Team-Connecticut, 2003. Presented at the 53 rd Annual Epidemic Intelligence Service Conference. Atlanta, GA. April, 2004.

19. Case-Control Study Sometimes, identifying a cohort is difficult –Members of cohort can’t be identified / contacted Case-control study is alternative

20. Case-control Studies Study Population Cases Controls No Exposure Had Exposure

21. Case-Control Study Steps in a Case-Control Study: 1.Identify the source population 2.Establish a case definition and select cases 3.Select controls

22. Case-Control Study Step 1 - Identify source population Represents the population that the cases came from; is similar to the cohort in a cohort study

23. Case-Control Study Step 2 – Establish a case definition and select cases A standard set of criteria for deciding disease status –Clinical criteria, time, place, and person

24. Case-Control Study Step 3 – Select controls Represent source population Collect same exposure information as for cases

25. Case-Control Study Step 3 – Select controls (cont’d.) Sources of controls –Random sample –Friends of cases

26. Cohort versus Case-Control

27. Study Design AdvantagesDisadvantages Cohort 1.Least prone to selection bias 2.Can reasonably conclude that cause preceded disease 3.Can study several diseases at once 4.Can examine rare exposures 5.Retrospective can be low- cost 1.Prospective can be expensive, time- consuming 2.Prospective can lead to loss to follow up 3.Exposed may be followed more closely than unexposed, yielding invalid conclusions about causality Case- Control 1.Less expensive and quicker than cohort 2.Can examine the effect of multiple exposures 3.Require a smaller sample population 1.Inefficient for studying rare exposures 2.Susceptible to selection bias 3.Cannot directly estimate the risk of disease 4.Cannot study several diseases at once

28. Matching in Case-Control Studies Makes one or more case and control attributes similar (e.g., age, gender, residence) An unmatched study design is usually preferred

29. Matching: Points to Consider More complex data analysis required Inability to assess role of matching factor on disease status –Do not match on exposure factor Potential for over-matching

30. Sampling Sampling is the systematic selection of a portion of the larger source population. A sample should be representative of the larger source population.

31. Sampling Why sample? Because it is more efficient – saves time and money!

32. Sampling Sample size Is the purpose of the study to determine the source of the outbreak? –A small number of cases and controls can reveal risk factors for infection. Is the purpose of the study to determine the number of persons who become sick over a specific period of time? –A cohort study would require a larger sample.

33. Sampling Types of sampling Simple random sample (SRS) Randomly select persons to participate in study. There are many variations of SRS. Convenience sample Choose those individuals who are easily accessible.

34. Sampling Problems with convenience sampling Based on subjective judgment Cases may or may not be representative of the total population May lead to biased results

35. Session II Summary An analytic study is used to test scientific hypotheses that may help support actions for specific control measures and to help prevent recurrence of a problem. A case definition with specific criteria helps you select your study population, as long as it does not include the hypothesis. Case-control studies, when conducted properly, are generally adequate and usually more efficient than cohort studies.

36. Session II Summary Cohort studies may be preferable when you work with confined (e.g., easily identifiable and accessible) study populations such as on a cruise ship or at a wedding reception. Case-control study controls need to be representative of the source population, and not matched on the exposure factor if matching is used.

37. References and Resources Begier EM, Barrett FK, Mshar PA et al. Body Shaving, Whirlpools, and Football: An Out break of Methicillin-Resistant Staphylococcus aureus Cutaneous Infections in a College Football Team-Connecticut, 2003. Presented at the 53 rd Annual Epidemic Intelligence Service Conference. Atlanta, GA. April, 2004. Centers for Disease Control and Prevention (1992). Principles of Epidemiology: 2 nd Edition. Public Health Practice Program Office: Atlanta, GA. Centers for Disease Control and Prevention "Gastroenteritis at a University in Texas" http://www.phppo.cdc.gov/phtn/casestudies/classroom/gastro.htmhttp://www.phppo.cdc.gov/phtn/casestudies/classroom/gastro.htm Gordis, L. (2000). Epidemiology: 2 nd Edition. W.B. Saunders Company: Philadelphia, PA. Gregg, M.B. (2002). Field Epidemiology: 2 nd Edition. Oxford University Press: New York. Hennekens, C.H. and Buring, J.E. (1987). Epidemiology in Medicine. Little, Brown and Company: Boston/Toronto.

38. References and Resources Iwamoto M, Hlady G, Jeter M et al. Shigellosis among Swimmers in a Freshwater Lake-Georgia, 2003. Presented at the 53 rd Annual Epidemic Intelligence Service Conference. Atlanta, GA. April, 2004. Kleinbaum, D., Sullivan, K., and Barker, N. (2003). ActivEpi Companion Textbook. Springer-Verlag: New York. Last, J.M. (2001). A Dictionary of Epidemiology: 4 th Edition. Oxford University Press: New York. McNeill, A. (January 2002). Measuring the Occurrence of Disease: Prevalence and Incidence. Epid 160 lecture series, UNC Chapel Hill School of Public Health, Department of Epidemiology. Morton, R.F, Hebel, J.R., McCarter, R.J. (2001). A Study Guide to Epidemiology and Biostatistics: 5 th Edition. Aspen Publishers, Inc.: Gaithersburg, MD. North Carolina Center for Public Health Preparedness. March 2005 Public Health Information Network session: “Descriptive and Analytic Epidemiology.” http://www.sph.unc.edu/nccphph/phtin/index.htm

39. References and Resources University of North Carolina at Chapel Hill School of Public Health, Department of Epidemiology, and the Epidemiologic Research & Information Center (June 1999). ERIC Notebook. Issue 2. http://www.sph.unc.edu/courses/eric/eric_notebooks.htm http://www.sph.unc.edu/courses/eric/eric_notebooks.htm University of North Carolina at Chapel Hill School of Public Health, Department of Epidemiology, and the Epidemiologic Research & Information Center (July 1999). ERIC Notebook. Issue 3. http://www.sph.unc.edu/courses/eric/eric_notebooks.htm http://www.sph.unc.edu/courses/eric/eric_notebooks.htm University of North Carolina at Chapel Hill School of Public Health, Department of Epidemiology, and the Epidemiologic Research & Information Center (September 1999). ERIC Notebook. Issue 5. http://www.sph.unc.edu/courses/eric/eric_notebooks.htm http://www.sph.unc.edu/courses/eric/eric_notebooks.htm University of North Carolina at Chapel Hill School of Public Health, Department of Epidemiology (August 2000). Laboratory Instructor’s Guide: Analytic Study Designs. Epid 168 lecture series. http://www.epidemiolog.net/epid168/labs/AnalyticStudExerInstGuid2000.pdf http://www.epidemiolog.net/epid168/labs/AnalyticStudExerInstGuid2000.pdf