Analytic Studies

ANALYTIC STUDIES

Dr. Sijal Fadhil Farhood Al-Joborae
F.I.C.M.S (Baghdad)
M.Sc. Comm.Med.(Nahrain)
M.B.Ch.B(Babylon)

introduction

The basic premise of analytic epidemiology is that disease does not occur randomly but rather in describable patterns that reflect the underlying etiology.
This rationale is certainly applied to case-control studies.
Consider two groups one in which every one has the disease of interest (cases) and a comparable one in which every one is free of the disease (controls).



The case-control study seeks to identify possible causes of the disease by finding out how the two groups differ. That is, because disease does not occur randomly, the case group must have been exposed to some factor, either voluntarily (eg. through diet , exercise, or smoking) . Or involuntarily(through such factors as cosmic radiation, air pollution, occupational hazard, or genetic constitution) that contribute to the causation of their disease.
Therefore a comparison of the frequency of exposure among cases and controls may permit inferences as to the basis for the difference in disease status.


Examples
Study to determine an association between autism and vaccination
Study to determine an association between lung cancer and radon exposure
Study to determine an association between salmonella infection and fast food restaurants

STRENGTHS:

1-Is relatively quick and inexpensive compared with other analytic designs.
2-Is particularly well suited to the evaluation of disease with long latent period.
3-Is optimal for the evaluation of rare disease.
4-Can examine multiple etiological factors for a single disease.

Limitation

1-Is inefficient for the evaluation of rare exposure 2-Cannot directly compute incidence rates of disease in exposed and non exposed individuals, but can estimate the relative risk(odds ratio)
3-In some situations the temporal relationship between exposure and disease may be difficult to establish.
4-Is particularly prone to bias compared with other analytic designs, in particular selection and recall bias.


Design of a Case-Control Study
Not Exposed
Exposed
Not Exposed
Disease
No Disease
“CASES”
“CONTROLS”

Exposed

Types of case-control study

If all the cases were already diagnosed at the time the investigator initiates the study, this is called Retrospective Case Control study.
If the study is begun and all the new cases that will be diagnosed within the next period of time will be included in the study it is called Prospective Case Control Study.


How to conduct case- control study
• Identify cases of disease of concern
• Identify appropriate non-diseased comparison group (“controls”)
• Document exposures among cases and controls
• Calculate odds ratios
• Perform statistical tests or calculate confidence intervals

In design ccs the major issues are:

1- select of case and control
2-the comparability of case and control is essential (matching) which is done to eliminate confounding factors
- group matching (eg:25% of case were married --25% of control were married)
-Individual matching (eg.:if the first case enrolled in a study is a 45year old white female--- control also 45year old white female)

3. accuracy and completeness of data , on the same level for cases and for control (measure of exposure)

4- analysis and interpretation .

Sources of Selection of the cases:
1. Hospital-based case control studies
The cases will be identified from the hospitals, or other health care facilities. These are common, relatively easy, and inexpensive.
2- Population based case-control studies.
It involves locating and obtaining data from all affected individuals or a random sample from a defined population.

Selection of cases

• specify definition of the disease or outcome
“strict diagnosis” appropriate
“case definition” and “
“diagnostic criteria” “should be made .

Source of selection of controls:

• Hospital control: consist of patients at the same hospital with conditions other than the disease under study.
In a CCS of association between cigarette smoking and MI among women .
Case : identify from admission to coronary care unit at particular hospital
Control: from admission to surgical , orthopedic and medical services of same institute (other than coronary disease)

2-General population control:

Used when the cases are chosen from the general population, and if the hospital control is not desirable or feasible.
3.Specific control series(friend, neighbor, relative).

Criteria of control

• Not having the disease being studied.
• Represents population from which cases arose.
• Represents persons who, if they develop disease, would have been a case in the study.
• Be selected independently of exposure.

Size of control:

we have to put in mind cost and feasibility aspect.
The optimal ratio of case to control is 1:1 (if the study group is large) but increasing control will increase the strength of study and 1:4 for instance especially if the number of cases are small.(1:2,1:3,1:4)

Types of bias in ccs:

Bias is not the reason to avoid ccs but to careful consideration of the source from which the bias may arise,and well designed and conducted ccs can provide a valuable information on the association between the disease and exposure.

Types of bias in ccs:

1.selection bias:
Arise from systematic differences in selecting the study groups
Eg:
-control selection bias(selection of an inappropriate control group)
-self-selection bias(non response or agreement to participate that is related to exposure and disease)


2.observational bias:
A- recall bias: the source of error depends on whether the cases remember exposures better than non-cases.
B- misclassification bias: There is an error in the classification of exposure or the disease

In general bias may affect the validity of the results by the possibility of exaggeration or under estimation.

MEASURES OF ASSOCIATION

Odds ratio:
is the ratio of the number of the ways the event can occur to the number of ways the events cannot occur.
It measures the association between exposure and outcome.

a

c ad
Odds Ratio = =
b bc
d



a
b
c
d
Case
Control
E+
E-

According to the table:

Proportion of cases exposed= a/a+c

Proportion of the control exposed= b/b+d

Proportion of the case non exposed = c/a+c

Proportion of the control non exposed = d/b+d

Interpret the Results
Odds Ratio = (15x10) / (20x5) =150/100
=1.5
• Cases
• Controls
• Total
• Exposed
• 15
• 20
35
• Unexposed
• 5
• 10
15
20
30
50


OR =1 (risk factor not related to the disease)

OR<1 (risk factor is actually protective factor against the disease)

OR>1 (risk factor positively associated with the disease

Example

A study of infertility found prior use of intra uterine devise(IUD) in 89 out of 283 infertile women.
In contrast 640 out of 3833 controls used IUD.
1-conduct 2x2 table.
2-what is the design of the study?
3-what are the advantages and limitations of this type of study?
4-Is there a relationship between infertility and the use of IUD? interpret it.

OR=(89x3193)/(640x194) =2.3 times more infertile women to be prior users of IUD than fertile women.Here the risk estimate shows a direct association between prior use of IUD and infertility.

case

control
total

infertile

fertile


IUD user
89
640
729
Non user
194
3193
3387
total
283
3833
4116