AETIOLOGY

Case control studies

(also RCT, cohort and ecological studies)

Objectives

Case control studydescribe structure and analysis interpret and calculate odds ratio identify potential for bias

10 year old girl, URTI Improved after taking aspirin

After several days, sleepy, vomited, lethargic, very confused, liver enlarged, blood aspartate and alanine transferase elevated

?

How assess cause(s)?

Case control study

CASE

CONTROL

EXPOSED

NOT EXPOSED

EXPOSED

NOT EXPOSED

Start

Case control studies

To assess the association between disease and exposure by comparing one group with the disease and the other without “Retrospective” study Disease status known History of exposure is unknown

Reye’s syndrome and medication useHalpin et al. JAMA 1982;248:687-91

All cases of Reyes syndrome in Ohio Dec.1978 - March 1980 (n=97)

Controls - children with similar viral illness from same schools as cases

Use of medication during illness Aspirin taken by 97% of cases vs only 71% of

controls Other medications similar in the 2 groups

Case control

CASE

Reyes syndrome

CONTROL

Recent viral illness

EXPOSED Aspirin

NOT EXPOSEDNo aspirin

EXPOSED Aspirin

NOT EXPOSEDNo aspirin

START

*Hypothetical case control study of Reyes syndrome and aspirin (unmatched)

Cases Controls Total

Aspirin used 190 130 320

No aspirin 10 70 80

Total 200 200 400

Why not relative risk/ risk difference?

"Outcome" Cases Controls Total Exposed

a b

Not exposed

c d

Total a+c b+d a+b+c+d

Odds ratio (OR)= Case / control ratio in exposed

Case / control ratio in non-exposed

= Exposed / non exposed ratio in cases

Exposed / non exposed ratio in controls

= a / b = ad / bc Ξ a /c = ad / bc

c / d b /d

= 190 x 70 / 10 x 130 = 10.2 (p < 0.05)

Interpret OR as for relative risk

Matched case control studies

Each case matched to 1 or more controls for selected confounding variables (usually age and gender, and sometimes other confounders) E.g. for a case aged 4 years, a control aged 4

years is selected Need to use matched analysis

OR = ratio of discordant pairs

Options for each matched pair

Case Exposed Not exposed Exposed Not exposed

Control Exposed Not exposed Not exposed Exposed

Control exposed

Control not exposed

Total

Case exposed

132 57 189

Case not exposed

5 6 11

Total 137 63 200

OR = ratio of discordant pairs= 57 / 5 = 11.4

Applications of case control studies

Etiologic research Vaccination effectiveness Outbreak investigation Occupational exposures Evaluation of screening Evaluation of treatment

Case control Advantages :

Efficiency : cost, time If rare disease Large number of exposures

Disadvantages : Cannot estimate incidence Susceptible to bias

Recall bias and selection bias Not suited for weak association

Strength of study types

ExperimentalRandomised controlled trial

Observational CohortCase-controlCross-sectionalEcologicalCase series

Confounding variable associated with outcome (disease)

and associated with exposure (risk factor)

risk factor

disease

confoundingvariable

Aspirin causes Reyes syndrome? Why important to distinguish between causal and

non causal associations? How distinguish between causal and non causal

associations? Epidemiological framework for causality

Aspirin causes Reyes syndrome?

Epidemiological framework for causality Other evidence?

aspirin no longer recommended for children use declined incidence of Reyes declined (reversibility

criterion)

SEE Causality lecture

Note, in children given aspirin, absolute risk is VERY low.