By
Dr. Nitya Krishna
2
nd
yr post graduate student
Public Health Dentistry
ANALYTICAL
EPIDEMIOLOGY
1
CONTENTS
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Introduction
Epidemiology
Classification of
epidemiological studies
Analytical epidemiology
Case control study
Basic steps
Bias
Advantages
Disadvantages
Cohort Study
Basic Steps
Bias in study
Advantages
Disadvantages
•Nested case control study
•Case cohort study
•Conclusion
•References
INTRODUCTION
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EPIDEMIOLOGY:
Epidemiology - Greek terms- “epi” - upon,
“demos” - people,
“logos” –study.
EPIDEMIOLOGY - the study of the distribution and
determinants of health-related states or events in specified
populations and the application of this study to control of
health problems.
JOHN M LAST 1988
ANALYTICAL EPIDEMIOLOGY
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Second major epidemiological studies.
Types of analytical study
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Two distinct type of observational studies.
Case control study
Cohort study
From each of these study designs, one can determine
a. Whether or not a statistical association exists
between a disease and a suspected factor.
b. If one exists, the strength of association.
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“Retrospective studies”, Trohoc study
First common approach to test the causal approach.
Distinct features:
Both exposure and outcome have occurred before the start of
study
Study proceed backward from effect to cause
Uses a control or comparison group to support or refute an
inference.
CASE CONTROL STUDY:
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Time
Direction of inquiry
Cases
(People with disease)
Controls
(People without disease)
Population
Exposed
Not Exposed
Exposed
Not Exposed
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BASIC STEPS IN CASE-CONTROL STUDY:
Selection of cases and controls
Matching
Measurement of exposure
Analysis and interpretation
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SELECTION OF CASES AND CONTROLS
SELECTION OF CASE
Case is a crucial to case control study
-Diagnostic criteria – Disease and stage of the disease -must
be specified
Eligibility criteria –
Sources -
SELECTION OF CONTROLS
Must be free from the diseases under study and similar to the cases as
possible.
Comparison group is identified before a study is done.
SOURCES
•Failure to select comparable controls can introduce “bias” in case
control studies.
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ii MATCHING:
Should be done to ensure comparability between cases and controls
Defined “ as process by which we select controls in such a way that they are
similar to the cases with regard to certain pertinent variables which known to
influence the outcome of the diseases and which, if not adequately matched
for comparability, could distort or confound the results ”.
CONFOUNDING FACTORS:
•Defined as “one which is associated with the exposure and the disease and is
distributed unequally in the study and control group”.
Eg: Smoking and alcohol in throat cancer, Age in oral cancer
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Several kinds of matching procedures.
a)Group Matching:
b)Pair Matching: Done by pairs
eg: 50 year old mason with a particular disease as case
50 year old mason without disease as a control.
If matching is overdone, it may difficult to find controls.
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iii) MEASUREMENT OF EXPOSURE
Information obtained should be same for both the cases and
controls
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iv Analysis and Interpretation:
a) Exposure rates
b) Estimation of risk
Exposure rates:
Direct estimation of exposure rates to a suspected factor in
disease and non disease groups.
Exposure rate is a /a+c = 94.2%
b/b+d = 67%
Cases with lung
cancer
Controls without
lung cancer
Smokers 33 (a ) 55 (b)
Non smokers 02 (c ) 27 (d)
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ESTIMATION OF THE DISEASE RISK
Relative risk or risk ratio – ratio between the incidence of disease
among exposed persons and incidence among non-exposed.
Incidence among exposed
Incidence among non-exposed
Odds ratio/ Cross product ratio is strength of association between
risk factor and outcome
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Odds ratio = a X d / c X b
33 X 27
55 X 2 = 8
Smokers have showed a risk of having lung cancer 8 times that of non
smokers
Cases with
lung cancer
Controls without
lung cancer
Smokers 33 (a ) 55 (b)
Non smokers 02 (c ) 27 (d)
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Dental amalgam and multiple sclerosis: a case-control study in Montreal,
Canada
Dental amalgams containing mercury have recently been suggested as a possible
risk factor for Multiple Sclerosis.
Case-control study conducted between 1991 and 1994, we interviewed a total of
143 MS patients and 128 controls, to obtain information on socio-demographic
characteristics and the number of dental amalgams and the time since installation
based on dentists' records.
Who had more than 15 fillings had an odds ratio (OR) of 2.57 compared to those
who had none; for individuals whose first amalgam was inserted more than 15 years
prior to the study, we found an OR of 1.34.
A suggestive elevated risk was found for those individuals with a large number of
dental amalgams, and for a long period of time.
Bangsi D et al; Int J Epidemiol1998;27(4):667-71.
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Dental erosion in asthma: a case-control study from south east Queensland
Asthma medication places patients at risk of dental erosion by reducing
salivary protection against extrinsic or intrinsic acids. But patterns of lesions in
asthmatics may differ from patterns in non-asthmatics, because gastro-
oesophageal reflux (GOR) is found in 60 per cent of asthmatics.
The lesions in 44 asthma cases were compared to those of age and sex match
controls with no history of asthma or medications drawn from the dental
records of 423 patients referred concerning excessive tooth wear.
Clinical differences were a higher incidence of tooth hypersensitivity,
xerostomia, salivary gland abnormalities, gastric complaints, and self induced
vomiting in the cases.
A higher incidence of erosion was found in asthmatics. The clinical
significance is that asthmatics are at risk of dental erosion from extrinsic acid,
but GOR does not appear to contribute in a site-specific manner.
Sivasithamparam K; Aust Dent J 2002;47(4):298-303.
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BIAS IN CASE CONTROL STUDIES
Bias “ is any systemic error in the determination of the association
between the exposure and the disease”.
Bias due to confounding
Information bias
Memory or recall bias
Telescopic bias
Interviewer’s bias
Selection bias
Prevalence or incidence bias
Berkesonian bias
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ADVANTAGES OF CASE CONTROL STUDIES :
Easy to carry out
Rapid and inexpensive
Require comparatively few subjects
Suitable to investigate rare disease
No risk to subjects
Allows the study of different etiological factors
No attrition problems and
Ethical problems minimal
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DISADVANTAGES OF CASE CONTROL STUDIES
Problems of bias
Selection of proper controls as difficult
Cannot measure the incidence rate
Do not distinguish between the cause and associated factors
Not suited for evaluation of therapy or prophylaxis
Representiveness of the cases and control
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COHORT STUDY
Another type of analytical study- done to obtain additional
evidence to support existence of an association between suspected
cause and disease
DISTINGUISHING CHARACTERISTICS:
•Cohorts identified prior to appearance of disease
•Study groups observed over a period of time – determine
frequency of disease
•Proceeds forward – cause to effect
COHORT STUDY
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Time
Direction of inquiry
People
without
disease
Exposed
Not Exposed
Population
Disease
No Disease
Disease
No Disease
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Cohort:
•Defined as - group of people who share a common characteristic or
experience within a defined time period.
Indications:
•Good evidence of association between exposure and disease
•Exposure is rare – but incidence of disease high among exposed
•Attrition of study population can be minimized
•Ample funds are available
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General considarations
Cohorts must be free from disease under study
Both groups should be equally susceptible to the disease
Both groups should be comparable with respect to the all
possible variables, which may influence the frequency of the
disease.
Diagnostic and eligibility criteria of the disease must be
defined beforehand.
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FRAME WORK OF COHORT STUDY
TYPES OF COHORT STUDIES:
On the basis of time of occurrence of disease in relation to the
time at which the investigation is initiated and continued.
Prospective cohort study
Retrospective cohort study
Combination of prospective and retrospective study
COHORT DISEASE TOTAL
Yes No
Exposed a b a+b
Non-Exposed c d c+d
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Elements/Steps in cohort study:
Selection of study subjects
Obtaining data on exposure
Selection of comparison groups
Follow up
Analysis
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SELECTION OF STUDY SUBJECTS:
General population
Group that can be readily studied
GENERAL POPULATION:
•If cause of death fairly frequent in population
•If population very large - Appropriate sample taken
SPECIAL GROUP:
Select groups:
Professional group
Government employees
Volunteers
Exposure group: exposure rare
E.g.: radiologists, workers in industries
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OBTAINING DATA ON EXPOSURE:
COHORT MEMBERS
Interviews/ questionnaires
REVIEW OF RECORDS:
Medical records – H/O surgery etc
MEDICAL EXAMINATION/ SPECIAL TESTS:
E.g: blood pressure, ECG etc
ENVIRONMENTAL SURVEYS:
To determine levels of exposure factor in environment
where cohort lived
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Information about exposure should be collected that will
allow classification of cohort members:
Whether or not they have been exposed to suspected
factor
According to level or degree of exposure
Demographic variables that may affect frequency of disease
under investigation
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SELECTION OF COMPARISON GROUPS:
INTERNAL COMPARISON: in-built study group
•From cohorts selected – one member enters study and rest
are comparative group
EXTERNAL COMPARISON:
•When information on degree of exposure not available
COMPARISON WITH GENERAL POPULATION RATES:
•When no information available
E.g.: frequency of cancer amongst asbestos workers with
general population in same geographic area
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FOLLOW UP:
Regular follow up required
It includes:
Periodic medical examination of each member of cohort
Reviewing physician and hospital records
Routine surveillance of death records
Mailed questionnaires, telephone calls, periodic home visits
Certain percentage of losses inevitable
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ANALYSIS:
Data analyzed in terms of:
•Incidence rate of outcome among exposed and non-
exposed.
•Estimation of risk
Relative risk
Attributable risk
RELATIVE RISK (RR) :
Measures strength of association between suspected cause and
association.
Incidence of the disease (or death) among exposed
Incidence of the disease among non-exposed.
a/a+c
b/b+d
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ATTRIBUTABLE RISK (AR):
•It indicates to what extent the disease under study can be
attributed to the exposure.
Incidence rates of disease among exposed group –non-exposed group
Incidence rates of disease among exposed group X 100
Suggests the amount of disease that might be eliminated if the
factor under study could be controlled or eliminated.
Attributable risk gives a better idea of the impact that a successful
preventive or public health program might have in reducing the
problem.
Cases with oral
cancer
Controls
without
oral cancer
Total
Smokers 70 (a ) 6930 (b) 7000 (a+b)
Non smokers 03 (c ) 2997 (d) 3000 (b+d)
DIFFERENCES BETWEEN RELATIVE RISK AND
ATTRIBUTABLE RISK
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RELATIVE RISK ATTRIBUTABLE RISK
Assess the etiological role of a
factor in disease
Does not assess the etiological
role of a factor in disease
Does not reflect the potential
public health importance
Reflect the potential public
health importance
Does not reflect the impact that
a successful preventive or
public health program might
have in reducing the problem
Better idea of the impact that a
successful preventive or public
health program might have in
reducing the problem
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Relationship Between Prehypertension/Hypertension and Periodontal
Disease: A Prospective Cohort Study.
The purpose of this prospective cohort study was to investigate whether
periodontal disease was related to prehypertension / hypertension in Japanese
university students.
The risk of hypertension was significantly associated with male, the risk of
prehypertension was not associated with presence of periodontal disease
A significant association between presence of periodontal disease and
hypertension was observed in Japanese university students
Kawabata Y; Am J Hypertens 2015; 23:125-128.
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BIAS IN COHORT STUDIES
Selection bias
Follow up Bias
Information bias
Confounding Bias
Post Hoc Bias
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ADVANTAGES:
•Incidence can be calculated
•Several possible outcomes related to exposure can be studied
•Provide direct estimate of related risk
•Dose response ratio can also be calculated
•Since comparison groups are formed before disease develops –
bias can be minimized
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DISADVANTAGES:
•Involve large number of people
•Unsuitable for investigating uncommon diseases
•Takes long time to complete study and obtain results
•Administrative problems: funding, keeping long records difficult
•Selection of groups is a limiting factor.
•Loss of cohorts – they may migrate, loose interest in study, refuse
to provide information
•There may be changes in standard diagnostic criteria of disease
over prolonged follow-up – difficult to introduce new knowledge
or techniques
•Study may itself alter cohort’s behavior
•Concentration on limited number of factors related to disease
outcome
•Study is expensive.
CASE CONTROL STUDY COHORT STUDY
1Retrospective “effect to cause”1Prospective “cause to effect”
2Disease has already occurred2Disease is expected to occur in
future
3Presence of exposure in cases and
controls compared
3Development of disease in exposed
and non –exposed compared
4Relatively easy to carry out4Time consuming and difficult to
carry out
5Useful for rare cases with smaller
number
5Suitable for common
diseases with common exposure
6Can only have one outcome, but
can have multiple exposure
6Can have multiple outcomes
7Only derives odds ratio 7Derives relative risk, attributable
risk etc.,
8Substantial biases can occur8Biases are generally lower
9Relatively less costly and no
dropouts
9Expensive and dropout rate higher
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NESTED CASE CONTROL STUDY:
Case control study - cohort study
Cohort of participants - baseline characteristics - interview, physical
examination and pertinent laboratory or imaging studies.
Cases - participants who develop the condition of interest
Control - participants who do not develop the condition of
interest
Cases and controls are studied and data from two groups are compared by
using analytical methods appropriate for case control study.
CASE COHORT STUDY:
Case control study in which source of population is a cohort – every person in
cohort has an equal chance of being included as controls - identified before any
cases develop, so some may later become cases.
Analysis for case cohort studies - more complex.
CONCLUSION
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Epidemiology helps to study the patterns, causes, and effects of
health and disease conditions in defined populations.
The analytical study is a non-experimental method of hypothesis
testing.
It is the ‘gold standard’ to test the association between the
exposure and outcome.
It is the cornerstone of public health, analytical strategies help in
developing scientifically sound health programs, interventions &
policies and evidence-based practice by identifying risk factors for
disease and targets for preventive healthcare.
REFFERENCES
44
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Katz DL, Elmore JG, Wild DMG, Lucan SC. JEKEL’S Epidemiology,
Biostatistics, Preventive Medicine and Public health. 4
th
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2014; 59 66.
Macmohan B, Trichopoulos D. Epidemiology principles and methods. 2
nd
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Spectrum publisher: New York: 1923; 165 - 299.
Dunning JM. Principles of Dental Public Health. Fourth Edition. Harvard university
press:1986 ;113-130.
Slack EL. Dental public health an introduction to community dental health. Second
edition. Stonebridge press; 1981: 86-118
REFERENCES
45
Jong. Community dental health. Fifth edition. edition.Elsevier publications; 2003:
173—185
Beaglehole R, Bonita R, Kjellstrom T. WHO Basic Epidemiology. Delhi: AITBS
publishers: 2006; 29 -39.
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