I is for Investigation

1
I is for Investigation
Outbreak Investigation Methods from Mystery to
Mastery
2
Session II

• Study Design

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Session Overview

• Developing and testing hypotheses
• Study designs
• Cohort studies
• Case-control studies
• Sampling

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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

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Basic Steps of an Outbreak Investigation

• Verify the diagnosis and confirm the outbreak
• Define a case and conduct case finding
• Tabulate and orient data time, place, person
• Take immediate control measures
• Formulate and test hypotheses
• Plan and execute studies
• Implement and evaluate control measures
• Communicate findings

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Developing and Testing Hypotheses

• Analytic Epidemiology

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Studies Assess Exposures and Outcomes

• Exposures refer to factors that might influence
  ones 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

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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

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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

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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

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Study Designs
Cohort studies and Case-control studies
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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, 3rd
  ed. New York Oxford University Press, 1995

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Cohort Studies
Study Population
Time Present
Exposure is self selected
Exposed
Non-exposed
Follow through time
Disease
No Disease
No Disease
Disease
Future
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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

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Identifying a Cohort

• Must be straightforward to define
• Must be at risk for disease

• Should not be selected so that everyone is
  exposed, or everyone is diseased
• Study group exposed
• Comparison group non-exposed

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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

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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.htm
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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. 2007143(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.

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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 53rd 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 53rd
  Annual Epidemic Intelligence Service Conference.
  Atlanta, GA. April, 2004.

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Case-Control Studies
Not Exposed
Not Exposed
Exposed
Exposed
Time Past
Cases
Controls
Study Population
Present
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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.

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Initial Steps in a Case-Control Study

• Identify the source population
• The population that the cases came from
• Similar to the cohort in a cohort study
• Establish a case definition and select cases
• A standard set of criteria for determining
  disease status that includes clinical criteria,
  time, place, and person

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Initial Steps in a Case-Control Study

• Select controls
• Controls represent exposure distribution of the
  source population
• Sources of controls
• Random sample
• Friends of case-patients

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Cohort versus Case-Control
Cohort Study Case-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 Group Exposed persons Persons with illness (cases)
Comparison Group Unexposed persons Persons without illness (controls)
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Study Design Advantages Disadvantages
Cohort Least prone to selection bias Can reasonably conclude that cause preceded disease Can study several diseases at once Can examine rare exposures Retrospective can be low-cost Prospective can be expensive, time-consuming Prospective can lead to loss to follow up Exposed may be followed more closely than unexposed, yielding invalid conclusions about causality
Case- Control Less expensive and quicker than cohort Can examine the effect of multiple exposures Requires a smaller sample population Inefficient for studying rare exposures Susceptible to selection bias Cannot directly estimate the risk of disease Cannot study several diseases at once
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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

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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

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Sampling
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What is sampling?

• The systematic selection of a portion of the
  larger source population. A sample should be
  representative of the larger source population.

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Why sample?

• Because it is more efficient saves time and
  money!

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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

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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.

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Problems with Convenience Sampling

• Based on subjective judgment
• Cases may or may not be representative of the
  total population
• May lead to biased results

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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

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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.

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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 53rd
  Annual Epidemic Intelligence Service Conference.
  Atlanta, GA. April, 2004.
• Centers for Disease Control and Prevention
  (1992). Principles of Epidemiology 2nd 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/classroo
  m/gastro.htm
• Gordis, L. (2000). Epidemiology 2nd Edition.
  W.B. Saunders Company Philadelphia, PA.
• Gregg, M.B. (2002). Field Epidemiology 2nd
  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 53rd 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
  4th 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
  5th 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.h
  tm

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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
• 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
• 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/traini
  ngpackages/ERIC/issue5.htm
• University of North Carolina at Chapel Hill
  School of Public Health, Department of
  Epidemiology (August 2000). Laboratory
  Instructors Guide Analytic Study Designs. Epid
  168 lecture series. http//www.epidemiolog.net/epi
  d168/labs/AnalyticStudExerInstGuid2000.pdf