STUDY DESIGN

By Hana. E(MPH)
Objectives

After completion of this session, the learner will:

1. Be able to classify study designs
2. Describe the characteristics of descriptive study designs
3. Design and describe the advantages and
limitations of cross-sectional, ecologic and
case report/series studies.
Cont….

4. Be able to classify analytical study designs

5. Describe the characteristics of analytical study designs
6. describe the advantages and limitations of cross-sectional, case
control, cohort and experimental study designs.
7. Design analytical studies
INTRODUCTION
Definition of design
• Design is an arrangement of conditions for the collection & analysis
of data that leads to the most accurate answer to the research
question and in the most economical way.
Classifications of study designs
1. Descriptive

• Defines the amount and distribution of health problems in

relation to person, place and time. It answers the questions
who, where and when.

2. Analytic

• involves explicit comparison of groups of individuals to

identify cause and determinants of health and diseases. It
answers the questions why and how 5
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Features of Descriptive Study

• Distribution of diseases with respect to time,

place and person.
• Useful for health managers to allocate resource
and to plan effective prevention programmes.
• Useful to generate epidemiological hypothesis in the
search for disease determinants or risk factors.
.
• Inexpensive and less time-consuming: can use
information collected routinely.
• Most common type of epidemiological study in the medical literature
Case Report and Case Series
• Documentation of unusual medical
occurrence
• First clue in the identification of new disease
or adverse effect of exposure
• Are the most common types of studies
published in medical literature/field
Case Report
• The profile of a single patient is reported in
detail by one or more clinicians
• Example
– a 40 years old women who developed pulmonary
embolism after beginning use oral contraceptive
• Example: Case report in 1961
A 30-year old lady developed gangrene of her fingers while
taking a drug for migraine headache.
• The investigator postulated that the drug may have been
responsible for this occurrence
Case Series
• Collection of individual case reports, which
occurs with in fairly short period of time.
• Helps in identifying the beginning or presence
of epidemic.
• Helps in hypothesis formulation
• But lack comparison group
• Describes the characteristics of a number of patients
with a given disease (same diagnosis).
• Example: Five young, previously healthy homosexual
men were diagnosed as having pneumocystis carinii
pneumonia at 3 Los Angeles hospitals during a 6
month period in 1980 to 1981.
• What is unusual in this case series? Until then this
form of pneumonia had been seen almost exclusively
among older men and women whose immune
systems were suppressed.
Strength and limitations of Case report and Case
series
Strength
• Very useful for hypothesis generation
Limitations
• Report is based on a single or few patients which can
happen just by coincidence
• There is no comparison group
• Lack of denominator to calculate rates of
disease
Cross-Sectional Studies

• A cross-sectional study is an observational

study in which exposure and disease are
determined at the same point in time in a
given population.
– The temporal relationship between exposure and
disease cannot be determined
Cross Sectional Studies: Time
• Time could be defined as:
– Time window: at the same calendar time.
 Meskerem 2003 E.C.
– Fixed point: varies in real time from person to
person.
 Pre-employment
Retirement
Admission to school
• Often difficult to establish temporal relationship between
exposure and outcome of interest.
Advantages of cross sectional studies:
• are a one-stop, one-time collection of data
• are less expensive
• provide much information useful for planning health
services and medical programs
• show relative distribution of conditions, disease, injury and
disability in groups and populations
• studies are based on a sample of a major population and do
not rely on individuals that present themselves for medical
treatment
Disadvantages of cross sectional studies:
• It is difficult to know which occurred first, the exposure or the
outcome. This is known as "chicken or egg dilemma".
Ecological study[ correlational
study]
• The units of analysis are populations or groups of people
rather than an individual.
• Ecological studies use data from the entire population to
compare disease frequencies between different groups
during the same period of time, or in the same population
at different points in time.
• Incidence and prevalence rates are commonly used to
quantify disease occurrence in groups.
• Does not provide individual data, rather presents average
exposure level in the Community
• Measures represent characteristics of the entire population
• Exposure and risk factors are known only at the group level
• Disease occurrence is at group level
Advantages of Ecologic Studies
 Aggregate data on exposure and disease are
often publicly available
 Aggregate level data can conveniently be
obtained by researchers at a low cost
Can be useful for evaluating the impact of
community-level interventions.
• useful to study exposures with minimal within community
differences but differ substantially
between communities, cities, states, and countries.
• Examples of small within-community exposure
differences but large between-community
differences include:
– Quality of drinking water
– Concentration of certain air pollutants such as ozone and fine
particles
– Average fat content of diet
– Cumulative exposure to sunlight
Limitations of ecological studies
1. Inability to link exposure with outcome at
individual level.
2. Lack of ability to Control potential confounders.
3. It represent average exposure levels rather
than actual values.
4. Ecological Fallacy.
The lack of individual-level information leads to
“Ecological fallacy” or “ecological bias”
In this fallacy an association observed between the
variables on an aggregate level does not necessarily
represent the association that exists at the individual
level
Ecological Fallacy
o Across level inference.
E.g. from group to individual.
• The ecologically fallacy
o Concluding that because an association exists
between exposure and disease at the group level it therefore
exits at the individual level.
o We don’t know the link between exposure and disease
among individuals with in each group
Ecologic Study (example)
Reynolds et. al., “Childhood Cancer and Agricultural
Pesticide Use An Ecologic Study in California ” Environ
Health Prospect (2002) 110:319-324
– Examined incidence of childhood cancers in California in
relation to pesticide use, 1988-1994
– Data sources: California Cancer Registry; U.S. Census;
California Dept. of Pesticide Regulations
– Looked at cancer of all types, and by specific types
– Found a significant association between childhood
leukemia rates in communities with highest use of
propargite
– No other associations were observed
Corelational (Ecological) Studies
The two key features that distinguish a traditional ecologic study
from other types of epidemiologic studies are:

1. The population unit of analysis

2. An exposure status that is the property of the population

Analytic study designs
Objectives
• After completion of this session, you will:
1. Be able to classify analytical study designs
2. Describe the characteristics of analytical study designs
3. describe the advantages and limitations of cross-sectional, case
control, cohort and experimental study designs.
4. Design analytical studies
 Analytic study designs

Analytic epidemiology
• Analytic epidemiology is the second major type of
epidemiology, which is concerned with analyzing the causes
or determinants of disease.
Analytic study designs
• focus on the determinants (causes) of diseases.
• Ultimate goal is judging whether a particular exposure
causes or prevents disease.
• Used to test hypothesis.
• The major difference from descriptive studies is Use of
controls.
Types of Analytic study designs

• Two major categories:

* Observational and
* Experimental
Observational analytic studies

• Case control and cohort studies are the commonest types of

observational analytic studies
Case control studies
Definition
• A case-control study is one in which persons with
a condition ("cases") and suitable comparison
subjects ("controls") are identified, and then the
two groups are compared with respect to prior
exposure.
• – subjects are sampled by their outcome status
• Subjects are selected with respect to presence or absence
of disease (outcome), and then inquiries are made about
past exposure to the factor of interest.
• Example: Is cigarette smoking a cause of lung cancer?
• Case control design: Identify people with lung cancer (cases) and
people without lung cancer (controls), and then ask both groups
whether they are/were smokers.
• If cigarette smoking is a cause of lung cancer, large proportion of lung
cancer cases will give history of cigarette smoking compared to the
normal individuals (controls)
Steps in conducting case control study
Step 1: Define cases
Step 2: Select cases
Places where we can get cases:
1.Hospitals (health institutions)
• Easy & inexpensive
• Selection bias is one of the major problems
2. Population (community)
-Expensive
-Avoids selection bias
Step 3: Select controls
• The controls should be similar with the cases except that
the cases have the disease or other outcome of
interest.
Sources of controls
• Hospital controls
Advantage:
• easily identified & readily available in sufficient
number
• less cost
• They are more likely to be cooperative
Disadvantages
• They are different from healthy individuals in many
ways
General population controls
Advantages:
• Generalization is possible
Disadvantage:
• Costly & time consuming
• Recall bias
• People might be less motivated to participate
Step 4: Check the exposure status of individuals both in
the cases and controls
• Information regarding the exposure status can be
obtained by interview or from different records.
Step 5: Analysis
• Prepare 2X2 table
• Calculate Odds Ratio (OR)
• Perform statistical tests to check whether there is
significant association
Advantages
o Useful for studying several potential exposures.
o Efficient for rare diseases.
o Efficient in resources and time
o Relatively quick, disease and exposure measurements
can be made at the same point in time.
Disadvantages
o Prone to selection bias and recall bias.
o Not suitable for rare exposures.
o May be difficult to establish that "cause”preceded
"effect”
Cohort studies

 Definition
An epidemiologic design that identifies
comparison groups according to their
exposure status.
‘A cohort’ Vs ‘Cohort study’

• A ‘cohort’ is simply a group of persons

with common characteristics who are
followed or traced over a period of time.

• ‘Cohort study’ is the analytical method

of epidemiologic study that compares
exposed and non-exposed groups.
Characteristics of a Cohort Study

•Groups of individuals defined on the basis of

presence/absence of exposure to the
suspected risk factor
•All potential subjects must be initially free of
the disease under investigation
•Eligible participants are then followed over
time to assess occurrence of disease
• Subjects are selected by exposure, or determinant of
interest, and followed to see the development of the
disease or other outcome of interest.
• Example: Is cigarette smoking a cause of lung cancer?
• Cohort design: Identify smokers (exposed) and non smokers (not
exposed) then follow both groups over time (e.g 10 years) and check
for development of lung cancer in both groups
• If cigarette smoking is a cause of lung cancer, large proportion of
smokers will develop lung cancer compared to the non-smokers.
Types of cohort studies
Classification of cohort studies depends on the temporal
relationship between the initiation of the study and the
occurrence of the outcome.

• Retrospective Cohort Study

• Prospective Cohort Study
Prospective Cohort Studies
•The investigator collects information on the exposure status
of the cohort members at the
time the study begins, and identifies new cases
of disease (or deaths) from that time forward
•The exposures may have occurred at the
beginning of study
•BUT the outcome has certainly not yet occurred
•After the selection of the cohort, participants must be
followed over time to assess incidence of disease.
Retrospective Cohort Studies
• Both the exposures and the outcomes have already
occurred when the study is initiated.
• Exposure status is established from information
recorded at some time in the past, and disease
incidence (or mortality) is determined from then until
the present.
• Example:
From medical records, identify a group of women who were using oral
contraceptives (OCs) 10 years ago and a group of women who were
not
• Either interview the women, or use medical
records, to determine their subsequent history
from that point to the present in terms of
developing heart disease.
o Retrospective: deals with current and past events;
can be done quickly
o Cohort: the comparison is made between users and
non-users of Ocs
Steps in conducting cohort study
Step 1: Define exposure
Step 2: Select exposed group
Step 3: Select non-exposed group
Step 4: Identify sources of data for exposure and
outcome
Possible sources of exposure data:
• pre-existing records
• conducting interview
Possible sources of outcome data:
• routine surveillance
• death certificate
• periodic health examination
• hospital records etc
Step 5: collect data
Step 6: Analyze data
• prepare 2X2 table
• calculate Relative Risk (RR)
• perform statistical tests to check whether there is statistical significant
association
Strengths and Weaknesses
Strength Weakness
• Can use prevalent cases
Uncertainty of exposure-
• Is inexpensive and quick to disease time relationship
complete
• Well suited for the evaluation Inability to provide a direct
of diseases with long-latency estimate of risk
diseases Very prone to biases (recall
• Can study rare diseases & selection bias)
• Can examine multiple Misclassification of
exposures exposures and outcomes
• Usually requires a smaller Selection of controls is
study population than a cohort difficult
study Inefficient for rare exposures
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 Cross sectional study
• The main purpose of cross sectional study to describe
occurrence of disease by time, place and person
• it can be considered as both descriptive and analytic
study design.
• The data collected by cross sectional study can be
analyzed in two ways,
• either by comparing the prevalent rate of the out come in
the exposed vs non-exposed people,
• or by comparing the prevalent rate of the exposure in
those with and without the outcome.
• One feature which distinguishes cross sectional study
from other types of observational analytical studies is the
timing of the subdivision of the study population into
comparison groups.
• In cohort and case control studies, this takes place prior
to the data collection process.
• In a cross sectional study, this takes place after the
information has been collected.
Experimental/ Intervention studies

• Individuals are allocated by the investigator.

• Can produce high quality data.
• Experiment is the gold standard study design compared to other
designs.
• Key Features of Experimental Design
1) Investigator manipulates the condition
under study
2) Always prospective
Classification of Intervention Studies
• There are different ways of classifying intervention
studies.
A. Classification based on the population studied
1. Clinical trial
 Usually performed in clinical settings and the
subjects are patients
2. Field trial
Used in testing medicine for preventive purpose
Subjects are healthy people e.g. vaccine trial
3. Community trial
Unit of the study is group of people/community e.g.
fluoridation of water to prevent dental caries
B. Classification based on design
1. Uncontrolled trial
No control group
Control will be past experience (history)
2. Non-randomized controlled
There is control group
Allocation to either group is not randomized
3. Randomized controlled
There is control group
There is random allocation of subjects to either group
C. Classification based on objective
1. Phase I
Trial on small subjects to test a new drug with small
dosage to determine the toxic effect
2. Phase II
Trial on small group to determine the therapeutic
effect
3. Phase III
• study on large population
• usually randomized controlled trial
Cont..
Phase III (effectiveness studies):
• Referred to as clinical trial
• Trial on large number of subjects (1000+) with therapeutic
dose to evaluate effectiveness of drug and side effects
• Usually randomized, blinded, controlled trial
• If successful, licensed and marketed
Phase IV
• Post marketing surveillance for long term effects.
• Large studies after approval of drug
• Often observational, study long-term effects
• Long term efficacy, rate of serious side effects
• Evaluate drug in “real life”, additional uses

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Problems related to experimental studies:
• Ethical considerations
Practices or substances already known to be harmful should
not be used in the study
Therapies known to be beneficial should not be withheld
from any affected individual
Investigator should have a complete knowledge of the
subject under study
Must have informed consent from each study participant
Subjects should left free to with draw from the study at any
time
A written research protocol is a must
• Feasibility/ practical issues
Include subject recruitment, getting adequate
individuals to enroll into the study is not easy
It is difficult to get satisfactory compliance
• Cost –very expensive
The Gold standard is achieved through:
• Randomization
• blindness
• Use of placebo
• Placebo - is an inert agent indistinguishable from the active
treatment given to the control groups
• Placebo effect - is the tendency of individuals to report favorable
response to any therapy regardless of the physiologic efficacy of what
they received
Steps in conducting experimental studies
1. Identify new drug/intervention/prevention
2. Identify comparison-e.g. standard treatment or
placebo
3. Define eligible populations/exclusions
4. Define the outcome and how to assess them
5. Write the protocol
6. Obtain research ethics committee approval
7. Recruit and consent required sample patients
8. Allocate individuals into :
experimental (study group): that will receive a drug ,
vaccine or other procedure
control group; that will receive no treatment, a
placebo, or standard form of therapy
9. Collect all relevant information including the outcome
10. Analyze the result. Analysis is similar to cohort study
11. publish/ disseminate the findings
Random allocation of subjects into experimental and control groups is
important.
Advantages of randomization:
• The potential for bias in allocation to study groups is
removed, it eliminates selection bias
• On average the study groups will be comparable
• confounders will be equally distributed ,controls
confounding effect ,
• study subjects will tend to be comparable with respect to all
variables except for the interventions being studied.
• favorable impression by those reading the published results
of a trial.
Advantages of Intervention Studies
• GOLD STANDARD: Randomized, placebo controlled,
blinded clinical trials
• The ability to assign exposure
• Findings can be replicated: Generalizability
• Prospective
• Clear temporal sequence
• Best evidence for causation
Disadvantages
• Unnatural situation
• Human behavior may be difficult to control
• Ethical constraints
• Exclusions may limit generalizability
• Expensive in time, personnel, facilities, and budget
Cont…

Uncontrolled trials

• The new intervention is studied without any direct comparison with a

similar group of patients on more standard therapy

• Problems of uncontrolled studies are:

-biased selection of participants

-biased assessment of outcomes

83
Cont…
Non randomized concurrent controls
• Non randomized methods are used to allocate participants to
intervention or control group
• Systematic allocation - e.g. date of birth, date of
presentation
• Judgement allocation – investigator or participant is allowed
to exercise judgement in allocation
• Major problem is predictability of allocation group,
especially by investigator

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Main steps in RCT
1. Identify new drug/intervention/prevention

2. Identify comparison –

Example, standard treatment versus placebo (Control v

intervention group)

3. Define eligible patient population/ exclusions (i.e the

sampling frame)

4. Define the outcomes and how to assess them

5. Write the protocol 85

cont…

6. Obtain research ethics committee approval

7. Recruit and consent required sample of patients

8. Randomize to treatment, then treat

9. Follow-up and compare/analyze outcome data

10. Publish/disseminate findings

86
Problems related to intervention trials
A. Ethical considerations

• Practices or substances known to be harmful should

not be used in this study.

• Therapies known to be beneficial should not be

withheld from any affected individuals.

• Investigators have to have a complete knowledge of

the subject.

87
Cont…

• Must have informed consent from each

• Subjects should be left free to withdraw

• A written research protocol is a must.

88
cont…

B. Feasibility/practical issues- volunteers, control

C. Cost of experimental studies

89
The Quality of “Gold Standard“ study design

The qualities that make experimental studies gold standard are:

 Randomization

 Blinding

 Use of Placebo

90
Randomization

• Maximize the chance of comparability of study groups at baseline

• Ideally, both groups are at the same stage of the natural history of
disease

• Ideally, only one factor affecting the outcome of interest would vary
between the study groups

91
Blinding…
• Single- blind is where only the study subjects do not
know who is getting the active intervention

• Double -blind is where study subjects and health care

giver do not know who is getting the active intervention

• Triple-blind is where the study subject, the field

investigator and the health care provider do not know
who is receiving the active treatment.

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Cont…
• Blinding procedures:

 Minimize bias related to assignment, assessment, or

compliance
 Minimize the potential for observation bias in
reporting of side effects and in assessing outcome
Minimize differential compliance

 Minimize differential loss to follow-up

 can be single, double or triple blind 93

placebo
• Placebos are inert treatments intended to have no
effect other than the psychological benefit of offering
treatment.

• Can only be used if there is no accepted treatment for

the condition under study.

• Use of placebo minimizes the bias in the

ascertainment of both subjective disease outcomes and
side effects. 94
Thank you