SLCM 2022 Case Control Study (SGD)

Prev Med Macabulos, Perez, Solano, Tapia

BLOCK #4 01/23/2018

OUTLINE B. USES OF CASE-CONTROL STUDY

I. SGD Proper • Test for risk factors
A. Framework of a Case-Control Study • Test for rare diseases
B. Uses of Case-Control Study → Ex. Test for relationship of promiscuity and Randyitis
C. Steps in a Case-Control Study § Outcome = Randyitis (rare disease)
II. Sample Case Control Study § Exposure = promiscuity
A. Guide Questions § Use case-control since Randyitis is a rare disease so it’s
B. Summary better to look for people already infected then check them
for promiscuity
OBJECTIVES • Test for multiple risk factors
• Describe the framework of a case-control study → Ex. Test for relationship of being a scholar, being
• Determine when to use a case-control study promiscuous, having 2 cars, and having gonorrhea
• Explain the requirements of a case-control study § Use case control because it’s hard to find subjects that fit
• Identify the advantages and disadvantages of a case-control study all criteria so it’s better to look for people already with
• Analyze and interpret the results of a case-control study gonorrhea then just check if they have those risk factors
§ Case-control allows the researcher/s to ascertain that not
I. SGD PROPER only one factor resulted to a patient contracting the
A. FRAMEWORK OF A CASE-CONTROL STUDY disease

C. STEPS IN A CASE-CONTROL STUDY

Sample study: Test for the relationship between social media use
and depression

1. Establish Case Definition

Figure 1. Framework of a case control study
• An analytic study
→ Tests for relationship between variables
→ Two types
§ Observational (ex. case control)
− No influence on the population
§ Experimental (ex. clinical trial)
• Observational analytic study wherein cases and controls,
diseased and non-diseased are identified, studied, and
compared with respect to prevalence of exposure or risk
factors
→ vs. Cohort
§ Subjects are exposed and non-exposed
§ Compared outcome
→ Case control: look back
→ Cohort: look forward
• Start at the level of outcomes—cases and controls
→ Cases: those with the outcome
→ Controls: those without the outcome
→ Retrospective
§ This means that at the start of the study, the outcome is
already known to the researcher. The exposure/s of both
the cases and controls is/are then traced back to identify
their association with the outcome
• Endpoint of a case-control study: if the prevalence of the
risk factor is greater in the diseased state
→ If so, it means that there could be a possibility that the
exposure is really the cause of the outcome
• Recruitment of sample population should be from a
homogenous population
• Objective: to identify the exposure (of both the cases and the
controls)
Trans #7 Group #30 : Tupaz, Valdez, Virtucio || Andres || Mateo
• Select your cases
→ Find people who are either depressed or non-depressed
→ Requirement: Cases should be representative of the disease
• How the disease is defined in your study
→ Has to be clear and specific
→ Otherwise, those that are not really cases could be included
and identified as cases
→ Example of a loose case definition: Asthma - difficulty
breathing, coughing
§ May include cases that are not asthma (ex: anxiety attack)
• Set your inclusion and exclusion criteria
• Be wary of selection bias when getting cases from hospital
→ Hospital cases are usually extreme cases
→ Doesn’t take into account asymptomatic cases
• Need homogenous group of cases to eliminate confounding
2. Choose your control group
• Be wary of selection bias
→ If you get your cases from the community, there’s a chance
you’ll get the neighbors, the associates, and the relatives of
your cases (not representative of the population)
• Requirement: Groups should be comparable to eliminate
confounding
• Where do you get your control?
→ Same-based population (i.e. both case and control should
come from the hospital)
• Ratio of cases to controls = 1:1 up to 1:4
→ Beyond 1:4 is statistically wasteful
• Matching with respect to confounders
3. Assess exposure
• Requirement: Assessment of exposure should be exactly
the same between case and control groups
• Through interview (recall bias), questionnaire (observer bias),
review of charts/documents
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4. Data analysis Doc Macabulos: Observation bias can be eliminated by using

• Compute for indicators or proportions hospital records because the researcher is supposed to have no
→ Social media and depression control on them – meaning the researchers just reads and records.
→ Social media and non-depression
• Measure of association in a case control study is via Odd’s II. SAMPLE CASE CONTROL STUDY
Ratio (OR) In a study conducted in Brazil, a group of researchers sought to
→ Measures strength of association between risk factors investigate whether specific morbidity due to chronic illnesses
→ The greater the value, the greater the association increased the risk of progression from Dengue Fever (DF) to
Dengue Hemorrhagic Fever/ Dengue Shock Syndrome
Table 1. 2x2 Table for Odd’s ratio Measurement for Case-Control (DHF/DSS).
Subjects were recruited in the Infectious Diseases Reference
Social Media Depression Hospitals in 6 identified cities during the epidemic years from 2009
(Exposure) + (Cases) - (Controls) to 2012. Designated as cases were patients with dengue fever
+ A B who progressed to DHF according to the WHO 1997 criteria: fever,
- C D hemorrhagic manifestations, thrombocytopenia (<100x109/L) and
evidence of plasma leakage (hematocrit change >20%
where, hypoproteinemia or clinical fluid accumulation), and one positive
specific laboratory diagnosis of dengue. Controls were patients,
! from the same hospital as cases, with signs and symptoms of DF
= probability of having the exposure among cases
!"# (fever, headache or retroorbiotal pain, myalgia, arthralgia,
prostration, exanthema, and positive specific diagnosis for dengue
# who did not progress to DHF.
= probability of not having the exposure among
!"# Laboratory investigation included Platelia Dengue NS1 Antigen
cases Kit and/or DENV IgM Capture by ELISA Kit. Past history of Dengue
was not established as prior serologic status (IgG) of the cases
$ and controls was not investigated.
= probability of having the exposure among controls
$"% Patients (and/or relatives) were interviewed by trained
interviewers using a previously tested, standardized questionnaire
% to obtain demographic and biological data (name, address, age,
= probability of not having the exposure among
$"% sex, self-reported skin color), socioeconomic indicators (years of
controls schooling and family income). Clinical information included signs
!
and symptoms of dengue, reported other health conditions
!&# (diabetes, hypertension, allergy, asthma) and use of medication for
# = !/# = exposure odds among cases control of these illnesses. Reports of co-morbidities were validated
!&# by asking for the name of person who made the diagnosis and
asking to see the prescription and/or packaging of any medication.
$
Only subjects able to show packaging or prescriptions were
$&%
% = $/% = exposure odds among controls considered to have the condition. Subjects were considered to
$&% have “allergy” if they reported allergy and provided evidence of
having used anti-allergic medication, including a prescription.
12345671 4%%5 !849: #!515
)**+ -./0) = Objective: To determine if chronic illnesses are risk factors for DHF
12345671 4%%5 !849: #49;74<5
A. GUIDE QUESTIONS
!/# !% 1. Examine carefully the case control study by Teixeira et. al
)- = =
$/% $# presented above. Was it a valid study? Give the bases for
your answer.
→ Check for the value of OR • In order to determine if the study was valid, assess the case
§ OR = 1 (risk factor of disease is equal to risk factor of non- control study based on the following requirements:
disease), no association between social media and → 1st Step: Case Definition
depression § Was the case defined concretely and clearly by the
§ OR > 1, there is association between social media and researchers?
depression § Did the researchers state the tool/s used to define the
§ OR < 1, people who use social media are less likely to case?
develop depression; social media acts as a protective § Is the criteria used a clinical, laboratory-based or both?
barrier § Different types of bias must be considered when defining
→ Compute for Confidence Interval (CI) the case.
§ Determines if the result is statistically significant § Researchers defined the case (DHF) in accordance to
§ Significant if null value of 1 is outside interval WHO 1997 criteria:
− Fever
Table 2. Advantages and disadvantages of case control studies − Hemorrhagic manifestations
Advantages Disadvantages − Thrombocytopenia
• Less time and resources • Prone to bias (selection, recall, − Evidence of plasma leakage
• Smaller sample size observation)
− One positive specific laboratory diagnosis for dengue
(compared to other studies) • Temporal ambiguity
- you don’t know which came first,
§ Moreover, the criteria that was used is both clinical and
• More economical
• Suitable for multiple the exposure or the outcome laboratory based.
exposures and rare diseases • Difficult to collect cases § Because the researchers defined the case clearly and
• Difficult to control confounders stated the tool they used, the study complied to the first
step.

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→ 2nd Step: Choosing of the right control
§ Cases and control must be comparable and must came
from the same population to eliminate confounding.
§ The control can be the sample size having or not having a
disease as long as this disease is not the case being
studies.
§ Ratio of case to control can be 1:1 up to 1:4. Any ratio out
of that interval is considered a not good proportion.
§ Control
− Patients with signs and symptoms of DF who did not
progress to DHF
− Criteria includes:
o Fever
o Headache/retroorbital pain
o Myalgia
o Arthralgia
o Prostration
o Exanthema
o Positive specific diagnosis for dengue
§ On this case control study, both the case and control
came from the same based population (that is from the
same hospital in 6 identified cities in Brazil) and can be
said as comparable.
→ 3rd Step: Assessment of Risk Factors
§ Variables related to exposure must be defined.
§ There are different ways to assess risk factors like
standardized questionnaire, interviews and review of
documents.
NTK: All analytic studies MUST have a table similar to Table 5
since it shows the comparison between the cases and control.
§ On this case control study, risk factors are assessed thru:
− Standardized questionnaire
− Interview
o Bias can occur during interview (recall bias and
observer bias)
− Asking clinical information (signs and symptoms of
dengue and other health conditions)
o Relatives, friends, and neighbors can be also part of
the data for control group, but they are most likely to
have the same exposure as that of the case group
o Reviewing of documents can also have bias
occurrence (Cases tend to have more complete
records)
− Asked for medications and prescriptions
§ Anything the researcher can do to minimize the type of
biases will strengthen the study.
→ 4th Step: Analysis of Data
§ Calculation of the frequency of each of the measured
variables in each of the two groups
§ On this case control study, the following tests were
utilized:
− Odd’s Ratio
o Measure of the strength of association between an
exposure and outcome
o Ratio of the odds of an exposure in the case group
to the odds of an exposure in the control group
− Confidence Interval
o For each odd’s ratio
o A confidence interval that includes 1.0 means the
association is not statistically significant or that the
association between exposure and outcome could
have been found by chance alone
o TH notes: Your confidence interval means that you
are N% sure (or N% confident) that your OR value
falls under this range
= Having the value 1.0 in the confidence interval
(ie. CI: x<1.0<y) means that there is a chance
that there is no association between the exposure
and the disease.
PREVENTIVE MEDICINE Case Control Study (SGD)
− P-value
o Test of significance
o If the computed p-value for a certain factor is less
than 0.05 (p<0.05), then the factor is said to be not
comparable
= TH note: In statistics, a p-value of <0.05 means
that you have to reject the null hypothesis (Ho:
there is no association between the exposure and
the disease), which entails that the exposure is
associated with the disease.
− Crude’s Ratio and Adjusted OR
o To eliminate confounders
− Logistic Regression
o To eliminate confounders
2. What is the purpose of the analysis of data shown in Table
[5]? Interpret the results.
• As shown in Table [5] (under Appendix), the researchers
showed:
→ Socioeconomic, demographic, and co-morbidity
characteristics of patients with DHF (case) and DF (control)
living in 6 municipalities of Brazil 2009-2012
§ Specifically, the researchers split the age of the population
into two: those who are under and above 15 years of age.
→ Sex, Age, Skin Color, Income, Schooling, Hypertension,
Allergy, Food allergy, Respiratory Allergy, Skin Allergy,
Diabetes, and Asthma
§ Here, the population were divided into different factors
and by the case and control selection
§ P-value was computed to show what factors are
statistically significant and comparable
− Based on the table, almost all the p-value of the risk
factors from those aged 15 and above group shows
comparison and significance
− Example: p-value of sex = 0.206 à greater than 0.05
(0.206 > 0.05) à insignificant
• Discussion:
→ The purpose of the analysis of data shown in Table [5] is to
show if there is a significant difference between the cases
and control in terms of sex, age, skin color, income,
schooling, hypertension, allergy, food allergy, respiratory
allergy, skin allergy, diabetes, asthma.
→ This table provided the values of population involved with
exposure to a disease and those who were not. Those which
are controls and those which are cases would be needed for
the computation of the odds ratio.
• One Sentence Statement: The cases were significantly of
mixed skin color, of lower income, and had no allergies.
3. Why was the analysis of data for the 3 variables of skin
color, family income, and skin allergy in Table [6] performed?
Interpret the results.
• Skin color, family income, and skin allergy all had a p-value of
less than 0.05 (see Table [6]).
→ Cases and controls were significantly different or not
comparable with respect to the 3 aforementioned variables
→ These variables are confounders
• Analysis on Table 6 was done to identify if the adjusted OR
done through logistic regression is able to address the
confounding property of the variables through checking of the
Confidence Interval of the adjusted OR
→ Ex. In Table 3, using the CI 95%, it can be surmised that only
income (its null value of 1.0 falls outside the CI range) is the
confounding factor unable to be adjusted even with using
other analytical techniques like linear regression
• Interpretation: Income is a confounder. The confounding
properties of the other 2 variables are addressed through their
adjusted ORs. It was checked whether they were confounders
through the use of the Confidence Interval.
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4. In reference to Table [7], show how the crude odds ratio were Adjusted Odds Ratio (OR)
obtained. Interpret the results. • A measure of odds ratio after considering all other possible
variables and eliminating confounding
Table 3. 2x2 Table for the Sample Case-Control Study
• Calculated using Logistic Regression
Cases Controls
HPN 90 217 Confidence Interval (CI)
Without HPN 226 690 • Estimates the precision of the OR
• Large CI, lower OR precision
ODDS RATIO = (90*690) / (217*226) = 1.3 • Small CI, higher OR precision

Interpretation: Adults with DF and hypertension are 1.3 times more

likely to develop DHF than those without hypertension. How to interpret Confidence Interval?
• The null value (i.e., OR = 1.0) is checked whether it falls within
5. What conclusion/s can you make from the study? the Confidence Interval.
• If it falls WITHIN the CI, the association is NOT statistically
Based on Table [7], hypertension and skin allergy are significantly significant.
associated with dengue hemorrhagic fever. → It means that the association between the exposure and
outcome could have been found by chance alone.
This can alert the physician to give more importance to those • If it falls OUTSIDE the CI, the association is STATISTICALLY
dengue patients with hypertension and skin allergy. For example, SIGNIFICANT.
they can be placed in special health units to ensure that in case they
go into shock, the physicians are ready. E.g., Among the diseases in Table 4, only Skin Allergy has its null
value (1.0) for the adjusted OR falling OUTSIDE the CI. The other
variables have their null value for the adjusted OR falling within the
B.SUMMARY CI. Therefore, among the four, only skin allergy is significantly
associated with DHF.
Crude Odds Ratio (OR)
How to interpret p values?
• A measure of association between the exposure and outcome
• At 95% CI, p value is at 0.05
• Represents the odds that an outcome will occur given a particular
• At 99% CI, p value is at 0.01
exposure, compared to the odds of an outcome occurring in the
• If not specified, it is always assumed that CI is at 95%.
absence of that exposure
→ If p value is less than 0.05, the following generalizations can
• Measure of ESTIMATED risk
be made:
• OR approximates relative risk ratio (in Cohort Studies) when the
§ The cases and controls are SIGNIFICANTLY DIFFERENT
disease is uncommon
(i.e., not comparable) with respect to a particular variable.
The association between the exposure and outcome are
Table 4. OR Interpretation
STATISTICALLY SIGNIFICANT.
If
Options Generic Interpretation
OR:
Harmful association
REVIEW: Steps in conducting a case control study:
Use OR value Those exposed are 1.5 times
(ex: RR=1.5) more likely to develop the
>1 1. State your epidemiologic hypothesis.
disease than those unexposed.
a. Define your variables
Subtract 1 from OR Those exposed are 50% more b. Identify your study population
(ex: 1.5 -1 = 0.5), then likely to develop the disease 2. Define and select your:
multiply value by 100 than those unexposed. a. Cases
1 Null value No association b. Controls
Beneficial association 3. Collect data and classify your participants according to
exposure status.
Subtract 1 from OR Those exposed are 50% less 4. Construct your contingency table.
(ex: 0.5 - 1 = - 0.5), likely to develop the disease 5. Analyze and interpret your data.
<1 then multiply value by than those unexposed. 6. Test for statistical significance using CI.
100
Take the inverse of Those unexposed are 2 times
the OR (divide 1 by more likely to develop the
REVIEW QUESTIONS
OR; 1/0.5 = 2) disease than those exposed.
True or False
1. Odds Ratio measures the strength of association and the
• TAKE NOTE: Odds ratio is NOT a test of statistical significance. statistical significance of estimated risk.
Rather, it measures the strength of association and estimated 2. As long as the OR is not equal to 1.0, there is a statistical
risk. association between the exposure and the risk.
• TIP: Before using the OR to measure the strength of association, 3. Case-Control Study starts with the exposure in the past and
make sure that the association is statistically significant first by then cases are identified if they have the disease at present.
using the Confidence Interval. 4. Lab tests done in the past should be verified with another set
• An odds ration without a Confidence Interval is not very of tests at the time of study.
meaningful. 5. A ratio of control:case = 1:4 is valid.

Aswers: F, F (always check the CI), F, F, F

PREVENTIVE MEDICINE Case Control Study (SGD) 4 of 5



APPENDIX
Table 5. Socioeconomic, Demographic, and Co-morbidity
characteristics of patients with DHF (case) and DF (control) living
in 6 municipalities of Brazil 2009-2012

Table 6. OR Values for Different Characteristics

Age group >/= 15 years
Charac- Crude CI 95% Adjus CI 95%
teristics OR -ted OR
Skin Color
White 1.0 1.0
Mixed 1.6 1.2–1.8 1.2 0.9–1.7
Back 1.1 0.7–1.7 0.8 0.5–1.2
Income
</= 1 1.0 1.0
2 </= 3 0.6 0.4–0.8 0.6 0.4-0.8
>/= 3 0.5 0.3–0.7 0.5 0.3-0.8
Schooling
0–3 1.0 1.0
4–7 0.6 0.3-1.0 0.6 0.3-1.0
8 – 10 0.7 0.4-1.1 0.8 0.5-1.3
>/= 10 0.8 0.5-1.2 1.0 0.6-1.6

Table 7. OR Values for Different Diseases

Chronic Crude CI 95% Adjusted OR CI 95%
Disease OR

HPN 1.3 0.9-1.7 1.6 1.1-2.1

Allergy 1.2 0.8-1.6 1.1 0.8-1.6

Food
Allergy 1.3 0.7-2.5 1.0 0.5-2.2

Skin
Allergy 1.8 1.1-3.0 1.8 1.1-3.2

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