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Study Designs

Cross-sectional

Case-control

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Study Designs

Observational Experimental

Case-control

Cohort

Cross-sectional

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Experimental Studies

• Produce the most scientifically rigorous data

• Difficulties enrolling subjects

• High costs

• Ethical issues

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Observational Studies

• “Natural experiments”

• Cross-sectional

• Case-control

• Cohort

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Cross-sectional design

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Cross-sectional study

• “Examines the relationship between diseases and other variables of interest as they exist in a defined population at one particular time.”

• Selection is independent of exposure or disease status.

• Done at a single point in time• Current disease status is examined in relation to

current exposure status• Carried out for public health planning and for

etiologic research

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CROSS-SECTIONAL STUDIES

• exposure and disease are assessed simultaneous in each INDIVIDUAL at a given point or SNAPSHOT in time...

ONE SLICE IN TIME

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CROSS-SECTIONAL STUDIES

• Because unit of analysis is INDIVIDUALS…

– Provides good estimate of Prevalence– NOT useful for rare events because in a

one-time snapshot enough rare diseases or rare exposures may not be captured (in ecologic studies samples sizes are always large!)

– May be subject to selection bias if certain INDIVIDUALS refuse to participate in the study for unknown reasons

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Key features of cross-sectional studies

• Examine association at a single point in time, and so measure exposure prevalence in relation to disease prevalence

• Cannot infer temporal sequence between exposure and disease if exposure is a characteristic

• Other limitations may include preponderance of prevalent cases of long duration and “healthy worker survivor effect”

• Advantages include generalizability and low cost

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CASE CONTROL STUDY DESIGN

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CASE CONTROL STUDIESSOME KEY POINTS

• Most frequently used study design

• Participants selected on the basis of whether or not they are DISEASED (remember in a cohort study participants are selected based on exposure status)

• Those who are diseased are called CASES

• Those who are not diseased are called CONTROLS

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Study Population

DISEASED non-DISEASED(Cases) (Controls)

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Study Population

DISEASED non-DISEASED(Cases) (Controls)

exposed non-exposed exposed non-exposed

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Because participants are selected on the basis of disease, exposures for ALL PARTICIPANTS are obtained RETROSPECTIVELY…

PAST PRESENT

Exposure recall Cases & ControlsSelected

Example: lung cancer cases and non-cancerous controls recall past exposure to cigarette smoke

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SELECTION OF CASES

• FIRST decide on a specific case definition based on a medically diagnosed condition

• Must consider what criteria will confirm the case definition– lung cancer confirmed by biopsy– osteoporosis confirmed by bone density

measurements– atherosclerosis confirmed by ultrasound

of carotid arteries

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SELECTION OF CASES• SECOND will you use INCIDENT or

PREVALENT cases?• Incident…

– must wait for new cases to occur– study can specifically measure exposure

relating to development of disease• Prevalent...

– don’t have to wait while cases occur with time - more practical!

– study will specifically measure exposure relating to survival with disease

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SELECTION OF CASES

• THIRD be aware of the unique qualities of certain groups– hospital admissions– nursing homes– screening participants– day care facilities

• some groups may have better supporting medical records

• some groups may be more homogenous and present less confounding variables

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SELECTION OF CONTROLS

• THE BIG PICTURE…

– Controls should be representative of the referent population from which cases are selected (I.e. comparable)

– They don’t have to be representative of the source (I.e. total) population

– Controls should have the potential to become cases (they have to be susceptible for the disease of interest)

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Total Population

Reference Population

Cases Controls

Controls should be comparable to cases

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Selection of controls

• Controls (referent group) are a sample of the population that produced the cases

• Controls come from the same base population as the cases

• Controls must be sampled independently of exposure status

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Sources of controls

1. Individuals from the general population

Advantage:Controls would be comparable to the cases w.r.t.

demographic variablesDisadvantage:1. Time consuming and expensive to identify2. Interest in participation3. Recall bias

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2. Individuals attending a hospital or clinic

• Illnesses of the controls should be unrelated to the exposure under study

• Control’s illness should have the same referral pattern to the health care facility as the case’s illness.

Advantages:1. Less expensive2. Easy to identify, good participation rates3. Have comparable characteristics to cases4. Recall of controls is similar to recall of cases

Disadvantage:Difficulty in determining appropriate illnesses for inclusion

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3. Friends or relatives identified by the cases

Advantage:• Share the cases’ socioeconomic status, race , age,

education etc..

Disadvantage:1. Cases may be unwilling to nominate controls

2. Bias results if cases and controls share a specific activity (exposure)

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4. Individuals who have died

• Deceased controls are used when some or all of cases are dead.

• Identified by reviewing death records of individuals who lived in the same geographic region and died during the same time period as the cases.

• Used to ensure comparable data collection procedures (proxy interviews)

Disadvantages:• May not be representative of the source population that

produced the cases• More likely to have used alcohol, drugs, smoking

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Sources of Exposure Information

• Questionnaires• In-person• Telephone interviews• Self-administered questionnaires• Medical records

Accuracy of the source especially that exposure is retrospective

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MEASURING ASSOCIATION

• because study participants in Case Control studies are selected based on disease status...

– case control studies are ideal for the study of rare diseases

– incidence can’t be calculated

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MEASURING ASSOCIATION

• Because incidence can’t be calculated, a relative risk can’t be calculated (RR is a ratio of INCIDENCE in exposed and non-exposed)

• Instead of the RR, an ODDS RATIO is calculated in case control studies

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Analysis of case-Control studies

• The size of the population which produced the cases is not known

• Can not calculate risk

• => calculate Odds

• The odds of an event is the probability that it will occur divided by the probability that it will not occur

• Disease odds ratio = Odds among the exposed

Odds among the non-exposed

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MEASURING ASSOCIATION

• Odds: NOT a proportion, but the ratio of the # ways an event CAN occur relative to the # of ways an event CAN NOT occur

Odds = P(event occurs) = p / ( 1 - p)1 - P(event occurs)

• Odds Ratio: Odds of case being exposed Odds of control being exposed

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Cases Controls

Exposed a b

Unexposed c d

Odds ratio= a/b

c/d

=ad

bc

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Is Use of Artificial Sweeteners associated with Bladder Cancer?

Cases Controls

Ever Used 1,2932,455Never Used 1,7073,321

Total 3,0005,776

ODDS RATIO = 1,293 * 3,321 = 1.026 2,455 * 1,707

Hoover and Strasser (1980) Lancet 1: 837-840

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Interpretation of the Odds Ratio…

IfO.R. = 1 then exposure NOT related to

disease

OR >1 then exposure POSITIVELY related to disease

OR <1 then exposure NEGATIVELY related to disease

Hoover and Strasser concluded what from their study?

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CASE CONTROL STUDY SUMMARY

Total population

Referent pop’n

cases

• cases and controls are representative of a referent population

• controls have the potential to become cases

• selection based on disease and exposure assessed retrospectively

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Twists and Turns in Case-

control Studies

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SELECTION OF CONTROLS

• The investigator can elect to use more than one TYPE of control for each case… when there is no ONE group similar enough to cases

EXAMPLE: a particular leukemia case may have both a neighborhood control (similar to case in terms of environment) and a sibling control (similar to case in terms of genetic background)

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SELECTION OF CONTROLS

• to avoid potential problems of confounding some studies use MATCHING

– MATCHING: the process of selecting controls so that they are similar to cases on certain specific characteristics

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Exposure Disease

Confounder

Confounders are third variables that are associated with both the disease and the

exposure

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SELECTION OF CONTROLS

• CHARACTERISTICS THAT ARE OFTEN USED FOR MATCHING…

– age– gender– body mass index (weight / height2)– smoking status– marital status

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BIAS IN CASE CONTROL STUDIES

BIAS: any systematic error (not random or by chance) in a study which leads to an incorrect estimate of the association between an exposure and the disease of interest

• MAIN TYPES of bias in Case Control Studies…– selection bias– recall bias

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BIAS IN CASE CONTROL STUDIES

• SELECTION BIAS: systematic error due to differences in characteristics between those selected for a study and those not selected

EXAMPLE in CC Studies: When cases are selected from a hospitalized population with unique exposures, controls often are not representative of the population that gave rise to cases

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BIAS IN CASE CONTROL STUDIES

• RECALL BIAS: systematic error due to differences in accuracy or completeness of recall to memory of past events or experiences

EXAMPLE in CC Studies: Often cases faced with a serious illness will more closely scrutinize their past exposures and will be more accurate and complete in their recall than controls

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What do you think will happen to our estimate of the Odds ratio if cases recall their exposure status better than controls?

D ND

Exposure a b

No exposure c d

Odds Ratio = ( a ) d / b c

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Strengths of case-control studies

• Efficient for rare diseases• Efficient for diseases with long induction

and latent periods• Can evaluate multiple exposures in relation

to a disease• can use smaller sample sizes• cost/time effective when using previously

collected (RETROSPECTIVE) exposures

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Weaknesses

• Inefficient for rare exposures• May have poor information on exposures because

retrospective• Vulnerable to bias because retrospective• Difficult to infer temporal relationship between

exposure and disease• can’t calculate incidence• selecting appropriate controls can be challenging

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When is it desirable to use case-control design?

• Exposure data are difficult or expensive to obtain

• The disease is rare

• The disease has a long latent period

• Little is known about the disease

• The underlying population is dynamic