TYPE OF EPIDEMIOLOGY STUDIES

Prof Dr. Noorliza Mastura Ismail

ProfDr. Abdul Rashid Hj. Ismail
Department of Community Dentistry
MMMC
 Objectives

At the end of this session, students are able to:

1. Classify the types of epidemiology studies

2. Explain the procedural steps and uses of each epidemiology study

 What is PICO?
Framing the Research Question: PICO (T)
Evidence-based models use a process for framing a
question, locating, assessing, evaluating, and repeating
as needed. PICO (T) elements include:
Problem/Patient/Population, Intervention/Indicator,
Comparison, Outcome, and (optional) Time element or
Type of Study.
P (Problem or Patient or Population): hospital ...
C (comparison): no hand washing; other soluti...
I (intervention/indicator): hand washing
A. Descriptive studies - describe occurrence of outcome
i. First phase of epidemiological investigation
ii.Observes distribution of disease/health-related characteristics in humans
iii.Identifies the associated characteristics of a particular disease

B. Analytical studies - describe association between exposure & outcome

i. Ecological or correlational - population as unit of study

ii. Cross-sectional/prevalence - individuals as unit of study
iii. Case control/case reference - individuals as unit of study
iv. Cohort/follow-up - individuals as unit of study

1. Define study population
2. Define disease under study •Operational definition of disease to describe occurrence & distribution
3. Describe disease by time,
place & person
4. Measurement of disease
5. Comparison with known
indices
6. Formulate etiological
hypothesis
A. Descriptive study
Procedural steps
•Whole population in geographic area or sample from population
•Select group - age, sex, occupation, hospital patients, school children
•Characteristic of population - large enough, stable
•Time – year, season, month, week, day, hour of onset, duration
•Place – climatic zones, country, region, urban, rural, town, cities,
institutions
•Person – age, sex, marital status, occupation, SES, education, birth
order, family size, height, weight, BP, personal habits
•Incidence (longitudinal studies)
•Prevalence (cross sectional studies)
•Comparison with other populations, within subgroups of same
population to identify high risk groups
•Studying distribution can arrive at hypothesis relating etiology
•Specify population, disease & expected outcome/relationship
 Study Design Sequence
Hypothesis formation
Descriptive
Case reports Case series
epidemiology

Analytic Animal Lab

epidemiology study study
Clinical
trials Hypothesis testing

Cohort Case- Cross-

control sectional
 Time frame of studies
• Prospective Study - looks forward, • Retrospective Study - “to look
looks to the future, examines future back”, looks back in time to study
events, follows a condition, concern events that have already occurred
or disease into the future

time
Study begins here
Increasing Knowledge of Descriptive Studies Develop hypothesis
Disease/Exposure

Case-control Studies Investigate it’s relationship

to outcomes

Define it’s meaning

Cohort Studies with exposures

Clinical trials Test the link experimentally

 Case Reports

• Detailed presentation of a single case or handful of cases

• Generally report a new or unique finding

• e.g. previous undescribed disease
• e.g. unexpected link between diseases
• e.g. unexpected new therapeutic effect
• e.g. adverse events
 Case Series
• Experience of a group of patients with a similar diagnosis
• Assesses prevalent disease
• Cases may be identified from a single or multiple sources
• Generally report on new/unique condition
• May be only realistic design for rare disorders

• Advantages
• Useful for hypothesis generation
• Informative for very rare disease with few established risk factors
• Characterizes averages for disorder
• Disadvantages
• Cannot study cause & effect relationships
• Cannot assess disease frequency
 Case Report One case of unusual findings

Case Series Multiple cases of findings

Descriptive Study Population-based cases with denominator

 Uses of descriptive epidemiology
1. Provide data – magnitude of disease load & type of problems in terms of
morbidity & mortality rates

2. Provide clues to disease etiology

3. Provide background data for planning, organizing & evaluating preventive

& curative services

4. Contribute to research by describing variations in disease occurrence by

time, place & person
 Study Designs - Analytical study
• Observational Studies
• Experimental Studies – Group data
• RCT • Ecologic
• Community trials
– Individual data
• Treatment & exposures occur in a • Cross-sectional
“controlled” environment • Cohort
• Planned research designs • Case-control
• Clinical trials are the most well-known • Case-crossover
experimental design. Clinical trials use • Non-experimental
randomly assigned data. • Observational because there is no individual
• Community trials use non-random data intervention
• Treatment & exposures occur in a “non-
controlled” environment
• Individuals can be observed prospectively,
retrospectively, or currently
 Association and causation

Association - the occurrence of 2 variables more often than would be expected by chance

Correlation - degree of association between 2 characteristics

Association can be grouped as:

1. Spurious association
2. Indirect association
3. Direct (causal) association –
a) one-to-one causal association
b) multifactorial association
 Cross-sectional Design
• An “observational” design that surveys
exposures & disease status at a single point
in time (a cross-section of the population) factor present
No Disease
factor absent
Study
population
factor present
Disease
factor absent

time
Study only exists at this point in time
 Cross-sectional Studies
• Often used to study conditions that are relatively frequent with long duration of
expression (non-fatal, chronic conditions)
• It measures prevalence, not incidence of disease e.g. community surveys
• Not suitable for studying rare or highly fatal diseases or a disease with short
duration of expression

• Disadvantages:
• Weakest observational design, (it measures prevalence, not incidence of disease), prevalent
cases are survivors
• The temporal sequence of exposure & effect may be difficult or impossible to determine
• Usually don’t know when disease occurred
• Rare events or quickly emerging diseases are a problem
 Case control study (Retrospective study)
Features:
1. “Observational” design - compare exposures in disease cases vs. healthy controls from same
population
2. Both exposure & outcome have occurred before start of study
2. Study proceed backwards from effects to cause
3. Uses control or comparison group to support or refute hypothesis
4. Involves two populations – case (with disease) & controls (no disease)
5. Unit of study is the individual
6. It is basically a comparison study
7. Cases & controls should be comparable to certain factors – age, sex, social status, occupation
8. Exposure data collected retrospectively
 Steps in conducting a Case-Control study
1 Selection of cases • Diagnostic criteria, Eligibility criteria, Source of cases – hospital, population
& selection of • Free from disease under study
controls • As similar to cases as possible except the disease under study
• Group identified before study, who have not been exposed to factors whose influence
is being studied
• Sources – hospitals, relatives, neighborhood, general pop
2 Matching • Ensure comparability
• Process of selection of control with similar to cases – age, sex which are known to
influence outcome
• Confounding factor – which is associated both with exposure & disease and is
distributed unequally in the case & control group.
• Neutralize confounding effect, protect against unexpected strong association between
matching factors & disease
• Pair matching or group matching

3 Measurement of • Interviews, questionnaire, past records

exposure
4 Analysis & • Exposure rate among cases & controls
interpretation • Estimation of disease risk associated with exposure (odds ratio)
 factor present
Case-Control Design
Cases
factor absent (disease)
Study
population
factor present Controls
(no disease)
factor absent
present
past

time

Study begins here

 Case-Control Study
• Strengths
• Less expensive and less time consuming
• Efficient for studying rare diseases
• Limitations
• Inappropriate when disease outcome for a specific exposure is not
known at start of study
• Exposure measurements taken after disease occurrence
• Disease status can influence selection of subjects
 Hypothesis Testing: Case-Crossover Studies

• Study of “triggers” within an individual

• ”Case" and "control" component, but information of both components will

come from the same individual

• ”Case component" = hazard period which is the time period right before the
disease or event onset

• ”Control component" = control period which is a specified time interval

other than the hazard period
 Bias in Case Control Studies

• Bias - any systematic error in the determination of association between exposure & disease
• Relative risk estimates may increase or decrease as a result of the bias, reflecting a non-
compatibility between the study and the control group

Types of bias
Confounding bias • Due to unexpected strong association between matching factor & disease
• Can be reduced by matching
Recall bias • Cases may recall better than controls who are healthy
Selection bias • Case and controls may not be representative of the population due to systematic
differences in characteristics between cases & controls
Berkesonian bias • Due to different rates of admission to hospitals for people with disease
Interviewer bias • May happen if interviewer is aware of the hypothesis or knows who the cases are.
May influence the degree of questioning more thorough than controls regarding a
positive history of suspected causal factor
• Can be eliminated by double-blinding
 Case control studies
Advantages Disadvantages
Relatively easy to carry out Problem of bias

Rapid & inexpensive Selection of appropriate control group

Suitable to investigate rare disease Cannot measure incidence, only relative risk

No risk to subjects Do not distinguish between causes & associated factors

Allow study of different etiological factors Unsuitable to evaluate therapy or prophylaxis of a disease

No attrition problem as follow-up not required Representativeness of cases & controls can be a problem

Minimal ethical issues

 Cohort Study
• Compare those with known risk factor/exposure & others without risk factor /exposure
• Looks at difference in the risk (incidence) of a disease over time
• Best observational design
• Analytical nature - evidence to refute/support association between cause & disease
• Done when there is good evidence of an association between exposure & disease
• Cohort – a grp of people who share common characteristics within a defined time period
• Also known as prospective, longitudinal, incidence or forward-looking study
• Cohorts are identified prior to appearance of disease under investigation
• Study groups are observed over a time period to determine frequency of disease among them
• Proceed from cause to effect
• Cohort must be free from the disease under study
• Study & control should be equally susceptible to disease under study
• Both groups are comparable with all variables which may influence frequency of the disease
• Diagnostic & eligibility criteria must be defined earlier
Strengths Limitations
-Exposure status determined before disease detection -Expensive & time-consuming
-Subjects selected before disease detection -Inefficient for rare diseases or diseases with long latency
-Can study several outcomes for each exposure -Loss to follow-up
Cohort Design
disease
Factor
present no disease
Study population
free of disease
Factor disease
absent
no disease

present
future

time
Study begins here
 Prospective cohort study
Prospective Study - looks forward, looks to the future, examines future events,
follows a condition, concern or disease into the future

Exposed Outcome

Measure exposure &

confounder variables

Baseline Non-exposed Outcome

time

Study begins here

 Retrospective Cohort study
• Retrospective Study - “to look back”, looks back in time to study events that have
already occurred

Exposed Outcome
Measure exposure
and confounder
variables
Non-exposed Outcome

Baseline

time
Study begins here
Activity:
Can you see the difference between
retrospective case-control & retrospective
cohort study?
Case-Control Study
 Steps in conducting cohort study
1. Selection of study subjects
General population • When exposure is fairly frequent, If population too large, sample identified
Special select group • Select groups maybe professional eg dentist, lawyer (Doll’s study - done among British doctors
listed in medical register 1951)
• Exposure groups if rare, more economical to select a known cohort who have experienced the
exposure eg radiologist exposed to x-rays
2. Obtaining data regarding exposure
Cohort members • Interviews, mail questionnaires
Review records • Radiation dose, type of surgery, treatment, exposure to risk factor eg. gutka chewing
Medical examination/special tests • Blood test, blood pressure, serum cholesterol, ECG
Environmental surveys • Exposure levels of suspected factor in environment where cohort lived/worked
3. Selection of comparison group
Internal comparison • Single cohort enters study, members may be grouped to compare, compare morbidity/mortality
External • When there is no data on degree of exposure, external control maybe required to evaluate
experience of exposed group eg tobacco chewers & non chewers
• Study & control grp should be similar in demographic & important variables except those under study
Comparison with • If no comparisons are available, then exposed group is compared to general population eg. frequency
general population of cancer among ceramic workers with rate in general population in the same geographic area.
 Steps in conducting cohort study (Cont)
4. Follow-up
a. Periodic medical examination of each member Attrition rate (percentage of losses)
- Inevitable due to death, change of residence,
b. Review hospital records
migration, withdrawal
c. Routine surveillance of death records - May cause bias in results
d. Mailed questionnaire, phone calls, periodic home visits etc - For good results, at least 95% follow up is necessary
5. Analysis
Incidence • Directly determined in those exposed & non exposed
rates
Estimation Relative risk (RR) Attributable risk Population-attributable risk
of risks - Ratio of incidence of disease among exposed & non- - Difference in incidence - Incidence of disease in
exposed rate of disease total population minus
- Direct measure of strength of association between between exposed & incidence of disease
suspected cause & effect non exposed among non-exposed to
- RR=1 suggest no association, RR>1 is positive - Indicate the extent of suspected causal factor
association, RR<1 is negative association disease that can be
- RR=2 indicate incidence rate 2X higher among exposed attributed to exposure
- The large the RR, the greater strength of association
between suspected factor & the disease

Advantages
1. Incidence can be estimated
2. Possible outcomes related to
exposure can be studied
3. Provide direct estimate of relative 3. Administrative problems – loss of expensive staff, funding, extensive
risk
4. Dose-response ratio can be
calculated
5. Certain biases can be minimized
Cohort studies
Disadvantages
1. Need large number of people (unsuitable for investigation of uncommon
disease)
2. Take longer time – patients/investigator may die, difficulty to keep large
number under medical surveillance
record maintenace
4. Loss of original cohort – migration, patients may loose interest in
study/refuse to give information
5. Comparison grp may not be representative of population
6. There may be changes in diagnostic criteria over time
7. Expensive
8. Study itself may change people’s behavior
9. Ethical issues
10. Practicality – limited number of factors related to disease outcome
 Compare & contrast
Case control study
1. Proceeds from effect to cause
2. Start with the disease
3. Tests if suspected cause occurs more
frequently in those with disease than
those without disease
4. First approach to testing hypothesis
5. Involve fewer subjects
6. Relatively quick results
7. Suitable for study of rare diseases
8. Yields only RR
9. Does not yield info about disease other
than the selected study
10. Relatively inexpensive
Cohort study
1. Proceeds from cause to effect
2. Start with people exposed to RF/suspected cause
3. Tests whether disease occurs more frequently
those exposed than in those not exposed
4. Testing of precisely formulated hypothesis
5. Involve large number of subjects
6. Long follow-up, delayed results
7. Inappropriate when disease/exposure under
investigation is rare
8. Yields incidence rate, RR & attributable risk
9. Can give info about more than one disease
outcome
10. Expensive
 Experimental epidemiology

• Involve some intervention/manipulation such as deliberate application or

withdrawal of the suspected cause or changing one variable in the
causative chain in the experimental group

Aims:
1. To provide scientific proof of etiological or risk factors which may permit the
modification or control of disease

2. To provide a method of measuring the effectiveness or efficacy of health

services for the prevention, control & treatment of disease
 Experimental Studies
• Investigator can “control” the exposure
• Akin to laboratory experiments except living populations are the subjects
• Generally involves random assignment to groups (randomization)
• Clinical trials are the most well-known experimental design
• The ultimate step in testing causal hypotheses

• In an experiment, we are interested in the consequences of some treatment on some

outcome.

• Subjects in the study who receive treatment of interest - treatment group.

• Subjects in the study who receive no treatment or a different treatment - comparison group.
 Animal studies
• Induce epidemics in animal under lab conditions
• Experimentally reproduce human disease in animals to confirm etiological hypothesis
• Test efficacy of preventive & therapeutic measures of vaccine/drugs & completing natural
history of disease

Advantages Disadvantages
1. Experimental animals can be bred in 1. Not all human disease can be
labs & manipulated according to needs reproduced in animals
of investigator
2. Experimental animals multiply rapidly 2. All conclusions derived from animal
experiments are not applicable to
humans
3. Ethical clearance available in many 3. Animal rights issues have been raised
countries
 Human experiments
• One best method to test preventive & therapeutic measures
• James Lind (1747) – citrus fruits in scurvy
• Edward Jenner (1796) – cowpox
• Finlay & Reeds (1881 – 1900) – mosquito home nature of yellow fever
• Issues are ethical & logistic considerations

2 types:
a. Randomized Control Trial (RCT)
b. Non-randomized/non-experimental trials
 Randomized Controlled Trials
• A design with subjects randomly assigned to “treatment” and “comparison” groups
• Provides most convincing evidence of relationship between exposure and effect
• Not possible to use RCTs to test effects of exposures that are expected to be harmful, for
ethical reasons
• “gold standard” of research designs
• Provides most convincing evidence of relationship between exposure and effect
e.g. Trials of hormone replacement therapy (HRT) in menopausal women found no
protection for heart disease, contradicting findings of prior observational studies

• Disadvantages
– Very expensive
– Not appropriate to answer certain types of questions
• it may be unethical e.g. to assign persons to certain treatment or comparison groups
 RANDOMIZATION
outcome
Experimental Design Intervention
no outcome
Study
population
outcome
Control
no outcome
baseline
future

time
Study begins here (baseline point)
What is randomization?
i. extensively used in human clinical trials & other biological experiments.
ii. prevents selection bias ie each patient has equal chance of receiving any of the treatments under study
iii. insures against the accidental bias
iv. produces comparable groups - ie. alike in all important aspects except for the intervention each group receives
v. eliminates bias in treatment assignments
vi. it permits use of probability theory to express likelihood of chance as a source for the difference of end outcome

Reasons for randomization:

1. Subjects in various groups should not differ in any systematic way. In clinical research, if treatment groups are
systematically different, research results will be biased. Suppose that subjects are assigned to control &
treatment groups in a study examining efficacy of a surgical intervention, if a greater proportion of older
subjects are assigned to the treatment group, then outcome of the surgical intervention may be influenced by
this imbalance. The effects of treatment would be indistinguishable from the influence of the imbalance of
covariates, thereby requiring researcher to control for covariates in the analysis to obtain an unbiased result.
2. It ensures no priori knowledge of group assignment (allocation concealment). Researchers, subject/patients
should not know to which group the subject will be assigned. Knowledge of group assignment creates a layer of
potential selection bias that may taint the data. Trials with inadequate or unclear randomization can over-
estimate treatment effects up to 40% compared with those that used proper randomization. Outcome of
research can be negatively influenced by this inadequate randomization.
Simple randomization
• This technique maintains complete randomness of the assignment of a subject to a particular group.
• Common & basic method of simple randomization - flipping a coin. For example, with two treatment groups (control versus treatment), the
side of the coin (heads - control, tails - treatment) determines the assignment of each subject. Other methods include using a shuffled deck of
cards (even - control, odd - treatment) or throwing a dice (<3 - control, >3 - treatment).
• Random number table or computer-generated random numbers can also be used for simple randomization of subjects.
• Simple & easy to implement in a clinical research.
• In large clinical research, simple randomization can be trusted to generate similar numbers of subjects among groups.
• Randomization results could be problematic in small sample size clinical research, resulting in an unequal number of participants among
groups.

Block randomization
• Designed to randomize subjects into groups that result in equal sample sizes.
• Ensure a balance in sample size across groups over time.
• Blocks are small & balanced with predetermined group assignments, which keeps numbers of subjects in each group similar at all times.
• The block size is determined by the researcher & should be a multiple of the number of groups (with two treatment groups, block size of either
4, 6, or 8).
• Blocks are best used in smaller increments as researchers can more easily control balance.
• After block size has been determined, all possible balanced combinations of assignment within the block (equal number for all groups within
the block) must be calculated.
• Blocks are then randomly chosen to determine the patients’ assignment into the groups.
• Although balance in sample size may be achieved with this method, groups may be generated that are rarely comparable in terms of certain
covariates. For example, one group may have more participants with secondary diseases (e.g., diabetes, multiple sclerosis, cancer,
hypertension, etc.) that could confound the data & may negatively influence the results of the clinical trial. Therefore important to control for
these covariates because of serious consequences to interpretation of results. Such imbalance could introduce bias in statistical analysis &
reduce power of study. Hence, sample size & covariates must be balanced in clinical research.
Stratified randomization

• It addresses the need to control & balance the influence of covariates.

• Used to achieve balance among groups in terms of subjects’ baseline characteristics (covariates).
• Specific covariates must be identified by the researcher who understands the potential influence each covariate has on the
dependent variable.
• Stratified randomization is achieved by generating a separate block for each combination of covariates, and subjects are
assigned to the appropriate block of covariates.
• After all subjects have been identified and assigned into blocks, simple randomization is performed within each block to assign
subjects to one of the groups.
• It controls for the possible influence of covariates that would jeopardize the conclusions of the clinical research. For example, a
clinical research of different rehabilitation techniques after a surgical procedure will have a number of covariates. It is well
known that the age of the subject affects the rate of prognosis. Thus, age could be a confounding variable and influence the
outcome of the clinical research.
• It can balance the control & treatment groups for age or other identified covariates.
• Although stratified randomization is a relatively simple & useful technique, especially for smaller clinical trials, it becomes
complicated to implement if many covariates must be controlled.
• Stratified randomization has another limitation - it works only when all subjects have been identified before group assignment.
However, this method is rarely applicable because clinical research subjects are often enrolled one at a time on a continuous
basis. When baseline characteristics of all subjects are not available before assignment, using stratified randomization is
difficult.
Covariate adaptive randomization
• One potential problem with small to moderate size clinical research is that simple randomization (with or without taking stratification of
prognostic variables into account) may result in imbalance of important covariates among treatment groups.
• Imbalance of covariates is important because of its potential to influence the interpretation of a research results. Covariate adaptive
randomization has been recommended by many researchers as a valid alternative randomization method for clinical research.
• In covariate adaptive randomization, a new participant is sequentially assigned to a particular treatment group by taking into account the
specific covariates and previous assignments of participants.
• Covariate adaptive randomization uses the method of minimization by assessing the imbalance of sample size among several covariates.
• Using the online randomization http://www.graphpad.com/quickcalcs/index.cfm, researcher can generate randomization plan for treatment
assignment to patients. Up to 10 treatments can be allocated to patients and the replication of treatment can also be performed up to 9 times.
The major limitations of this software is that once the randomization plan is generated, same randomization plan cannot be generated as this
uses the seed point of local computer clock and is not displayed for further use. Other limitation of this online software Maximum of only 10
treatments can be assigned to patients. Entering the web address http://www.graphpad.com/quickcalcs/index.cfm on address bar of any
browser, the page of graphpad appears with number of options. Select the option of “Random Numbers” and then press continue, Random
Number Calculator with three options appears. Select the tab “Randomly assign subjects to groups” and press continue. In the next page, enter
the number of subjects in each group in the tab “Assign” and select the number of groups from the tab “Subjects to each group” and keep
number 1 in repeat tab if there is no replication in the study. For example, the total number of patients in a three group experimental study is 30
and each group will assigned to 10 patients. Type 10 in the “Assign” tab and select 3 in the tab “Subjects to each group” and then press “do it”
button. The results is obtained as shown as below (partial output is presented)
• Another randomization online software to generate randomization plan is http://www.randomization.com. The seed for the random number
generator is obtained from the clock of the local computer & is printed at bottom of the randomization plan. If a seed is included in the request,
it overrides the value obtained from the clock & can be used to reproduce or verify a particular plan. Up to 20 treatments can be specified. The
randomization plan is not affected by the order in which the treatments are entered or the particular boxes left blank if not all are needed. The
program begins by sorting treatment names internally. The sorting is case sensitive, so the same capitalization should be used when recreating
an earlier plan. Example of 10 patients allocating to two groups (each with 5 patients), first the enter the treatment labels in the boxes, and enter
the total number of patients that is 10 in the tab “Number of subjects per block” and enter the 1 in the tab “Number of blocks” for simple
randomization or more than one for Block randomization.
 Steps in RCT
1. Draw protocol – details of study
2. Select referenced study population -
3. Randomization - the practice of using chance methods
(random number tables, flipping a coin, etc.) to assign
subjects to treatments
4. Intervention
5. Follow-up
6. Assessment of outcome
 Types of bias in assessment
Bias - any systematic error in the determination
of association between exposure & disease

I. Subjective bias - Participants who may subjectively feel better /report

improvement if they knew they were receiving a new form of treatment

II. Observer bias – Investigator measuring the outcome maybe influenced if he

knows beforehand the particular therapy to which the patient was subjected

III. Evaluation bias – Investigator may subconsciously give a favorable report of

outcome of trial. Randomization alone cannot prevent these biases. Thus
blinding is done
 How to reduce bias
i. Single blind – trial is planned where participants are not aware whether he belong to
study or control group

ii. Double blind – neither doctor nor participant aware of group allocation & treatment
received

iii. Triple blind – doctor, participant & statistician not aware of groups or treatment allocation

Type of trial Participant Investigator Statistician

Single blind X / /
Double blind X X /
Triple blind X X X
X - Blind & / - Aware
 Types of experimental study design
Concurrent parallel design
• Comparisons are made between 2 randomly assigned grps – exposed & not exposed to
specific treatment
• Patients remain in the same study grp till end of investigation either study or control group

Cross-over type of design

• Each patient serves as his own control
• Patients are assigned randomly into study & control group
• Study group receive treatment while control receive placebo
• Groups are observed for certain period, then they are taken off medication – wash out
period
• Group receiving treatment are then switched to control & vice versa
• All patients assured of receiving new therapy some time during investigation.

*This method is unsuitable if drug of interest cures the disease, drug is effective only during
certain stage of disease or disease changes radically during period of study
 Non-randomized control trials
RCT not always possible due to:
• Ethical/administrative reasons
• Some preventive measures can be applied to groups/community
• Require long time
• Expensive because disease frequency low or natural history is long
Types of non-randomized trials
1. Uncontrolled trials – useful in initial evaluation whether a specific therapy has value in a particular disease or
to investigate adverse reaction

2. Natural experiments – since experiments not possible in human, epidemiologist seeks to identify natural
circumstances eg smokers, non-smokers, migrants, religious or social groups, families, earthquakes

3. Before & after comparison

Without control – Prevention of scurvy among sailors (Lind, 1750) by providing citrus fruits, the experiment
itself serves as control
With control – Utilize natural control group. If program is applied to entire community, investigator selects
another community with similar disease frequency & characteristics
 References:
• Murray JJ, Nunn H, Steele G. Prevention of Oral Diseases. Oxford: Oxford University
Press; 2003
• Daly B, Watt R, Batchelor P, Treasure E. Essential Dental Public Health. Oxford: Oxford
University Press; 2002
• Hiremath SS. Textbook of Preventive and Community Dentistry. 2nd edition Elsevier
India; 2011
• Gluck GM, Morganstein WM. Jong’s Community Dental Health. Mosby St Louis;
2003.
• Pine CM and Harris R. Community Oral Health. 2nd edition Quintessence; 2007