Study Design:

CASE-CONTROL STUDIES

Dr. Daniel C. OSHI

Department of Community Health & Psychiatry

5/6/2019 Daniel C. Oshi 1

 Learning Objectives
• By the end of this module, you should be able to:
• Define case-control study and the main types.
• Define and explain what cases and controls are, as well as their
sources.
• Describe the basic steps involved in case-control studies
• Calculate and interpret odds ratio from case-control studies

5/6/2019 Daniel C. Oshi 2

 Introduction
The risk factor (exposure) is the
independent variable while
the outcome is the
A case-control study is a research dependent variable.
strategy that seeks to assess the
degree of association between a
risk factor (an exposure) and an In this sense, case-control
studies are similar to cohort
outcome.
studies, but more resource-
efficient.
5/6/2019 Daniel C. Oshi 3
 Types of Case-control Studies
Case-control studies could be:

Retrospective case-control study: All the cases have already occurred

by the time the participant enrollment is commenced.

 Nested case-control studies: This is a case-control study which is

“nested” within a cohort study. In this type, the participants in the
cohort study form the source population for the case-control study.

5/6/2019 Daniel C. Oshi 4

 Case-control Studies
As the name suggests, there are two arms in case-control studies:

 The cases: This arm is made up of individuals who have the disease or
event of interest.

 The controls: This arm consists of individuals who share similar

characteristics with the cases but do NOT have the disease or event of
interest.

5/6/2019 Daniel C. Oshi 5

 Case-control Studies
So,
a case-control study compares individuals who have the disease or event
of interest (i.e. the cases) with individuals who do not have the disease
or event of interest (i.e. the controls),

and then,

retrospectively (looking back) assesses the extent to which each group

was exposed to a risk factor.
5/6/2019 Daniel C. Oshi 6
 Case-control Studies

By so doing, the case-control study assesses the relationship between the

risk factor (exposure) and the disease (event) of interest.

5/6/2019 Daniel C. Oshi 7

 Case-control Studies

Exposed
Disease CASES

Not exposed

Exposed
No disease CONTROLS

Not exposed

5/6/2019 Daniel C. Oshi 8

 Cases vs Controls
Cases Control
• Cases are defined as individuals who have the • Controls are individuals who have similar
disease of interest. For example, women who social, demographic and clinical characteristics
have breast cancer. as the cases except that they do not have the
• But it should be clear how diagnosis is made. disease (event) of interest.
In other words, when and how do you say a
woman has breast cancer? • They must be selected from the same source
• Must it be by histological diagnosis? population as the cases.
• If, YES, then any woman without a histological
diagnosis of breast cancer is excluded.
• Cases should be recruited from a defined
source population
5/6/2019 Daniel C. Oshi 9
 Where do we recruit our cases from?

Health facility-based Cases: Hospital or clinic records are used to identify

suitable cases (individuals who have the disease of interest).

Population-based Cases: Less frequently, cases may be selected from the

source population using disease registries. In such instances, random
sampling is used to select a representative sample from the population.

5/6/2019 Daniel C. Oshi 10

 Where do we recruit our controls from?
 Health-facility-based controls: If your cases were recruited from a health
facility, the controls should also be recruited from patients in same health
facility who have similar characteristics but not the disease of interest.

Recruiting from same health facility may introduce bias, and thus, you can
recruit from the source population.

 Population-based controls: If the cases were recruited from the source

population through random sampling, the controls should also be
recruited from the same source population through random sampling.
5/6/2019 Daniel C. Oshi 11
 Case-control study: Basic Steps
Hypothetical example:

Assessing the strength of the association between alcohol consumption

and breast cancer among women in Kingston.

Research Question:
Is alcohol consumption a risk factor for developing breast cancer among
women in Kingston?

5/6/2019 Daniel C. Oshi 12

 Case-control study: Basic Steps
RECRUITING THE CASES in the hypothetical example:

Identify ‘ALL’ women aged 15 – 75 years who have histological diagnosis

of breast cancer (e.g. at UHWI) (these are your cases).

Then, from the cases:

Identify women who consume alcohol (exposed cases)
Also, identify women who do not consume alcohol (unexposed cases)

5/6/2019 Daniel C. Oshi 13

 Case-control study: Basic Steps
RECRUITING THE CONTROLS in the hypothetical example:
Controls should be selected without consideration of their exposure status.
However, subsequently, we sub-classify them into:
• Exposed controls
• Non-exposed controls.
From the sample of controls:
Identify women aged 15 – 75 years who do not have histological diagnosis
of breast cancer but who drink alcohol (exposed controls).
Identify women aged 15 – 75 years who do not have histological diagnosis
of breast cancer and do not drink alcohol (non-exposed controls).
5/6/2019 Daniel C. Oshi 14
 Matching
• Matching is a systematic way of ensuring that the controls and
cases closely resemble each other in every aspect except that
the controls do not have the disease of interest .
• Matching helps to minimize biases and confounding
Some of the features you match for include:
• Age
• Sex
• Being at risk for the disease of interest
5/6/2019 Daniel C. Oshi 15
 Approaches to Matching
Individual matching: For the key variable you want to match,
you select one or more (1 to 4 usually) individuals without the
disease of interest but who match a case on the variable.

Case #12: female, Age 24 years; for control, you select a female,
exactly 24 years (or if you are matching to 2 years, the control
could be between 22 and 26 years)

5/6/2019 Daniel C. Oshi 16

 Approaches to Matching

Frequency matching: The cases are matched with controls by

distributions of characteristics, e.g. age groups.

For example, if 40% of the cases are aged 30 years and below,
then 40% of your controls should also be 30 years or below.

5/6/2019 Daniel C. Oshi 17

 Computing the odds ratio for our hypothetical example
Typically, in c-c study, we are interested in assessing the odds of exposure
among the cases relative to the odds of exposure among controls.
 Odds of exposure among cases:
Number of cases with exposure ÷ Number of cases without exposure
 Odds of exposure among controls:
Number of controls with exposure ÷ Number of controls without exposure

Odds ratio =
Odds of exposure among cases ÷ Odds of exposure among controls

5/6/2019 Daniel C. Oshi 18

 Odds ratio

2 x 2 Table for Odds Ratio

Outcome Exposed Not exposed Total

Disease A B A+B

No disease C D C+D

Total A+C B+D A+B+C+D

5/6/2019 Daniel C. Oshi 19

 Odds ratio

2 x 2 Table for Odds Ratio

Odds of exposure among cases A÷B

Odds of exposure among controls C ÷D

Odds ratio = Odds of exposure among cases A÷B = A/B

Odds of exposure among controls C ÷D C/D

5/6/2019 Daniel C. Oshi 20

 Computing the Odds Ratio
Exposure No exposure

Cases 16 92

Controls 7 64

Odds of exposure (compute) = +

Odds of exposure among cases =

Odds of exposure among controls =

Daniel C. Oshi 21
5/6/2019
 Computing the Odds Ratio
Exposure No exposure

Cases 16 92

Controls 7 64

Odds of exposure = 16/ 92 = 0.1739 7/64 = 0.1094

Odds ratio (OR) = Odds of exposure among cases / odds of exposure among controls
= 0.1739/ 0.1094 = 1.59

Daniel C. Oshi 22
5/6/2019
 Computing the Odds Ratio
Exposure No exposure

Cases 16 92

Controls 7 64

Odds of exposure = 16/ 92 = 0.1739 7/64 = 0.1094

Compute Odds ratio (OR) = Odds of exposure among cases / odds of exposure among controls

Daniel C. Oshi 23
5/6/2019
 Computing the Odds Ratio
Exposure No exposure

Cases 16 92

Controls 7 64

Odds of exposure = 16/ 92 = 0.1739 7/64 = 0.1094

Compute Odds ratio (OR) = Odds of exposure among cases / odds of exposure among controls

OR = 0.1739/ 0.1094

Daniel C. Oshi 24
5/6/2019
 Case-control Studies
Strengths:
o Useful with small sample of cases
o Requires less time, money and human resource.
o Good for investigation of rare diseases
o Can be used to investigate multiple exposures
o Used to initially establish association between an exposure and a
disease/ outcome

5/6/2019 Daniel C. Oshi 25

 Case-control Studies
Weaknesses:
o Weak for estimation of incidence rate
o Weak in estimation of causal relationships.
o Selection bias is inherent
o Case definition can lead to exclusion of useful cases.
o Recall bias if investigating exposures that require recall (for example,
alcohol consumption, dietary habits)

5/6/2019 Daniel C. Oshi 26