1. I is for Investigation Outbreak Investigation Methods from Mystery to Mastery

2. Session II Study Design

3. Session Overview Developing and testing hypotheses Study designs –Cohort studies –Case-control studies Sampling

4. Learning Objectives Understand how to develop and test a hypothesis about an exposure and an outcome Describe the design of cohort studies and case control studies Learn how to assess which study design to apply during an outbreak investigation Explain the rationale and options for sampling in an outbreak investigation

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 hypotheses 6.Plan and execute studies 7.Implement and evaluate control measures 8.Communicate findings

6. Developing and Testing Hypotheses Analytic Epidemiology

7. Studies Assess Exposures and Outcomes Exposures refer to factors that might influence one’s risk of disease –Examples Smoking Eating at a particular restaurant Outcomes refer to case definitions –Individuals who have the specified disease/condition of interest –Examples Small cell carcinoma Laboratory diagnosis of Campylobacter

8. What is an Epidemiologic Hypothesis? An educated guess about an association between an exposure and an outcome that is testable in a scientific investigation Data from descriptive epidemiology provide information to develop hypotheses Hypotheses tend to be broad initially and are then refined to have a narrower focus

9. Example Broad 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 Narrower 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

10. Analytic Studies Designed to test an epidemiologic hypothesis: –Is there an association between exposure and disease? –How strong is the association? Two types used in outbreak investigations: –Cohort –Case-control

11. Study Designs Cohort studies and Case-control studies

12. 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

13. Cohort Studies DiseaseNo Disease Study Population ExposedNon-exposed No DiseaseDisease Exposure is self selected Follow through time Time: Present Future

14. Cohort Study Types A cohort study analyzes an exposure / disease relationship within the entire cohort Prospective –Identified population is followed forward through time –The Framingham Study Retrospective –Exposure is documented and cohort is “followed” for outcomes that have already occurred –Usually used in outbreak investigations

15. Identifying a Cohort Should not be selected so that everyone is exposed, or everyone is diseased –Study group: exposed –Comparison group: non-exposed Must be straightforward to define Must be at risk for disease

16. When to Use a Cohort Study Design 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 CDC Vessel Sanitation Program, 2012. http://www.cdc.gov/nceh/vsp/surv/GIlist.htmhttp://www.cdc.gov/nceh/vsp/surv/GIlist.htm

18. Cohort Study Examples Skin disorders among Hurricanes Katrina and Rita reconstruction workers –Enrolled civilian construction workers living and working at a New Orleans military base Noe R, Cohen AL, Lederman E, et al. Skin Disorders Among Construction Workers Following Hurricane Katrina and Hurricane Rita: An Outbreak Investigation in New Orleans, Louisiana. Arch Dermatol. 2007;143(11):1393-1398. Gastroenteritis on a Greek island during a religious festival –All island residents were enrolled Karagiannis I, Detsis M, Gkolfinopoulou K, Pervanidou D, Panagiotopoulos T, Bonovas S. An outbreak of gastroenteritis linked to seafood consumption in a remote Northern Aegean island, February-March 2010. Rural and Remote Health 10: 1507. (Online) 2010. Available: http://www.rrh.org.au.

19. 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.

20. Case-Control Studies Study Population CasesControls Not Exposed Exposed Time: Past Present

21. When to Use a Case-Control Study When the study population is hard to define When the study population is difficult to contact When the study population is very large When the outcome is rare A case-control study is the alternative to a cohort study.

22. Initial Steps in a Case-Control Study 1.Identify the source population –The population that the cases came from –Similar to the cohort in a cohort study 2.Establish a case definition and select cases –A standard set of criteria for determining disease status that includes clinical criteria, time, place, and person

23. Initial Steps in a Case-Control Study 3.Select controls –Controls represent exposure distribution of the source population –Sources of controls Random sample Friends of case-patients

24. Cohort versus Case-Control Cohort StudyCase-Control Study Best when…Members are easily identifiable Members are easily accessible Exposure is rare There are multiple diseases of interest Source population is not easily defined Accessing entire cohort would be too costly or time consuming Illness is rare Study GroupExposed personsPersons with illness (cases) Comparison GroupUnexposed personsPersons without illness (controls)

25. 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.Requires 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

26. Matching in Case-Control Studies Matching attributes are “third factors” –Age, gender, residence Can clarify relationship between exposure and outcome Unmatched study design is usually preferred

27. Matching: Points to Consider Special analytic techniques required Cannot assess role of matching factor on disease status –Do not match on a potential exposure Over-matching may result in not representing source population

28. Sampling

29. What is sampling? The systematic selection of a portion of the larger source population. A sample should be representative of the larger source population.

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

31. 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

32. 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.

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

34. Session II Summary An analytic study is used to test scientific hypotheses A case definition with specific criteria is used to identify cases from the study population, and should not include the study hypothesis Cohort studies provide a direct estimate of the risk of disease, whereas case-control studies do not

35. Session II Summary Cohort studies may be preferable when you work with easily identifiable and accessible study populations Case-control studies, when conducted properly, can be an efficient alternative to cohort studies Controls should represent the source population, and not be matched on the exposure factor if matching is used.

36. References and Resources Begier EM, Barrett FK, Mshar PA et al. Body Shaving, Whirlpools, and Football: An Outbreak 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.

37. 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. University of North Carolina at Chapel Hill Gillings School of Global Public Health, UNC Center for Public Health Preparedness, and the NC Institute of Public Health. E is for Epidemiology. Session 3: Descriptive and Analytic Epidemiology; 2012. Available from: http://cphp.sph.unc.edu/trainingpackages/E/index.htm http://cphp.sph.unc.edu/trainingpackages/E/index.htm

38. 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://cphp.sph.unc.edu/trainingpackages/ERIC/issue2.htm http://cphp.sph.unc.edu/trainingpackages/ERIC/issue2.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://cphp.sph.unc.edu/trainingpackages/ERIC/issue3.htm http://cphp.sph.unc.edu/trainingpackages/ERIC/issue3.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://cphp.sph.unc.edu/trainingpackages/ERIC/issue5.htm http://cphp.sph.unc.edu/trainingpackages/ERIC/issue5.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