Study designs in medical

research

Dr. Nashwa Radwan

Professor of Public Health and
Preventive Medicine
‫بسم ال الرحمن الرحيم‬
Learning Objectives
 To understand the concepts of
different study designs
 To learn about the advantages and
disadvantages of several study
design.
 To be able to choose the best
study design to assess certain
health problem.
 What is research?
 Research is the manner by which
we attempt to solve problems or to
conform the validity of the
solutions to problems
Purpose
 The basic aim of clinical research is to
advance knowledge of human health
and illness .
1-Assess the health status or clinical
characteristics of a well defined
population
 the annual rate of suicide in teenager .

 The incidence of rabies in certain

locality.
2-Probe the natural history of the disease
…
 The clinical course of retinopathy in
Examine clinical decision- making processes …
 The best screening test for glaucoma in
general population.

4-Determine and assess treatment outcomes . …

 Tumor response of laryngeal cancer in patients
who receive radiation .

5-Identify and assess risk factors

 The incidence of lung cancer in smokers
relative to non smokers
Principles used in
:assessing such data
 Efficacy: describes the true treatment or
intervention effect under ideal condition
 Effectiveness :describes the true treatment
or intervention effect under routine condition .
 Reliability : describes the reproducibility of
the test results .
 Bias : is a systematic error that is
unintentionally made .
 Sensitivity :describes test positives or true
abnormal correctly identified .
 Specificity : describes test negatives or true
normal correctly identified .
 What the types of
epidemiological studies?
 Observational
Experimental

 Use an existing  Test the effect of some

phenomena in attempt to
understand aspects of intervention on a
health or illness . The certain aspect of health
investigator neither or illness . The
control the population nor investigator can control
the factors to which the
population is exposed . both the population and
 a-Case report study. the factors to which the
 b-Case series study. population exposed .
 a-Cross sectional or
prevalence study.  a-Single blind.
 b-Retrospective or case-
control study.  b-Double blind.
 c-Prospective or incidence  c-Trible blind.
study.
Types of Epidemiologic
Observational Studies

based on:
 type of sampling from population -

based on Exposure &/or Disease or

neither
 temporal sequence of observation

- one time point, forward,

backwards
Types of Studies
A. Experimental - study factor is
manipulated by the investigator
Types
1. Pure versus Quasi-experimental
2. Laboratory versus real world
B. Observational - no manipulation of
study factor by the investigator
1. Descriptive versus Analytic
2. Retrospective versus Prospective
 A-Case report
-Description
 Is a brief objective report of clinical
characteristic or outcome from a single
clinical subject or event
-Study question :
 It is commonly used to report unusual or
unexpected events
-Examples:
 A report of advanced diabetic retinopathy in
a patient with no other clinical evidence of
diabetes .
-
Methodology

 A single event first must be identified .

 Data collection generally is retrospective

,with a review and a descriptive summary of

subject or event .
 No statistical analysis or comparative group

is included
-Strengths and limitation :
 It provides the first report of unexpected

event, hypotheses for testing and definition of

issue for further study. But the results are
rarely generalized
B-Case series report:
-Description:
 An objective report of a clinical
characteristics or outcome from a group of
clinical subjects .
-Study question :
 Report new diseases or health related
problems .
-Examples :
 Is one that identified several children with
birth defects who were born to mothers who
had taken thalidomide.During pregnancy.
-.
-Methodology :
 Subjects must be identified with regard to the

clinical characteristics
 Data collection may be retrospective or

prospective , but a control or comparison

group is not included
 Descriptive statistics are calculated

- Strengths and limitations :

 Generalization of the results is limited because

; the selection of study subjects is

unrepresentative and lack of comparison
group
 Cross-Sectional Study –
Prevalence Study
 Description
 Cross-Sectional Studies measure
existing disease and current exposure
levels.
 This study analyzes data collected on a
group of subjects at one time rather
than over a period of time The method
of research that simply looks with
intense accuracy at the phenomena of
the moment (what is happening? Right
now) and then describes precisely what
the researcher sees.
 The point should be clearly emphasized that
looking or seeing is not restricted to
perception through the physical eye. In
research we have many ways of seeing;
examples
 -The physician looks at the heart through a
stethoscope and electrocardiogram.
 -The educator and the psychologist look at
intelligence, attitude, believes through IQ
tests, attitude scales and other evaluation
scales.
 -The epidemiologist looks in survey through
interview and questionnaire.
 sample without knowledge of
Exposure or Disease
 sample at one point in time
 Mostly prevalence
studies/surveys
-Study question:
 Concern the occurrence of the

disease and the rate of other events

In a single point of time( the
prevalence)
-Example:
 The rate of occurrence (prevalence)

of smoking among high school

students at a particular point of time.
Methodology:
 The population for the study must be
carefully chosen, clearly defined.
 Target population is surveyed at a
single (particular) point of time (e g. one
year)..
 The rate of occurrence of diseases and
events among the target population in a
particular point of time (e.g.the
prevalence) is calculated.
 No statistical analysis is included.
 Strengths and Limitations:
-It is quick, cheap and easy
-True rates are determined (the prevalence).
- The prevalence rate is used as a measure

of health status in the population of

interest and for comparisons between
different populations and communities.
- Can study multiple exposure and multiple

diseases.
 Impractical for rare diseases
 Not a useful for establishing
causal relationships. It does not
allow us to answer the question
,which came first (which caused
which)
 No control over sample size for
each exposure by disease
subclass.
 Data are particularly
susceptible to distortion
through the introduction of bias
How Bias Enters the Research
Design

 Example:
 A researcher decides to use a city
telephone directory as a source for
selecting a random sample.He will open
a page at a random, close his eyes, put
the point of the pencil down on the
page, and the names that comes to the
pencil point will be selected.you can not
get much more random than that. But
the evil spirit of bias is there. HOW?
D- Case – control study –
Retrospective Study:
-Description :
 An observational study in which
diseased and non- diseased (controls)
subjects are identified after the fact and
then compared regarding specific
characteristics to determine possible
association of risk for the disease .
--
 Case-Control Studies identify
existing disease/s and look back in
previous years to identify previous
exposures to causal factors.
 Analyses examine if exposure
levels are different between the
groups.
 Cases are those who have a
disease.
 Controls are those without a
disease.
 look back in previous years to
identify previous exposures to
causal factors.
Study question :
 Address the issue relating to risk factors

for disease by comparing the effect of a

particular factor in diseased population
to that in non-diseased population .
-Examples :
 Comparing the rate of smoking in

normal subjects and patients with lung

cancer.
Methodology
 Find cases of the disease and obtain from
them or about them the history of the
assumed cause exposure.
 Find control persons similar to the cases,
and similarly obtain histories of exposure
from them.
 Statistical analysis is done between both
groups to determine that the difference
between two groups is real not to chance .
 Conclusion are useful for generation of
hypotheses and for initial evidence of risk
association
Strengths and limitation
-Cases are easily available (usually hospital
based) . Thus, its the method of choice for rare
diseases.

-Historical data are often available from clinical

records of patients, So it is possible to use
these data without obtaining further
information from case or controls.

- It is quick and cheap as the disease of interest

has already occurred.

-It tends to support, but not prove, causal

hypotheses by establishing associations of risk
factor.
-Bias in data collection:
- The study is un masked. ( since the presence
or absence of disease is known to the subject
and the observer).
-Recall bias may also occur because exposure
to risk factor is often dependant on memory of
subjects.

-Bias in the selection of subjects :

(Non-representative ness of cases) since a case
control study is not population – based such
fallacy is called( Berkson Fallacy).
-The occurrence of the assumed cause is
obtained from the history of the selected cases
and controls Thus we can not know which
occurred first? (Which Caused Which) .
E- Cohort –Prospective-
Incidence Study

-Description :
 It is an observational study in which
exposed and non exposed population are
identified and followed prospectively over
time to determine the rate of a specific
disease or event .
-Study question :
 Address issues relating to risk factors by
comparing population exposed to a factor
under study to population that are not
exposed .
-Examples:
 The incidence of lung cancer in smokers to
nonsmokers .
 Exposed and non exposed
population.
 Follow prospectively over time.
 Measure the incidence rate.
Methodology
a-A population of exposed and non
exposed must be determined and
followed prospectively for a certain
period of time(e.g. one year)
b- Exposure to risk factor under study.
c-The incidence rate of disease or an
event for both exposed and non
exposed must be calculated and the
relative risk is measured .
d-Statistical comparison is made between
exposed and non exposed to assess
that the observed difference is real not
due to chance
Strengths and limitation

-Costly and time consuming due to the need for

large number of subjects and prolonged time
of follow up
-Potential bias in recall and selection is lessened
-Allows study of rare diseases.
-The results is considered more conclusive than
case- control study
-Allows for determination of a population –based
rate of new disease or event(e.g.the Incidence
Rate) and the Relative Risk .
 How do we calculate the
Incidence Rates(IR)?
 How do we calculate the
Relative Risk(RR)?
F- Clinical trial :
-Description :
It is an experimental study used to assess
the differences between two or more
groups receiving different
interventions or treatments .
-Study question :
To compare outcomes between different
intervention .
Examples

A comparisons between chemotherapy to

chemotherapy plus radiation for
laryngeal carcinoma .
Testing different types of vaccines on
population of children to prove their
efficacy in preventing the diseases.
-Testing different forms of health service
delivery.
-Types:
-Single blind:When the studied persons do
not know whether they belong to the
treatment or the control group.
-Double blind: When this knowledge is not
known by both the studied persons and
the experimenter.
-Triple blind:When this knowledge is not
known by all the three parties; the
studied persons, the experimenter, and
the statistician.
 -Methodology :
a-A population with a clinical characteristic
requiring intervention must be
determined .
b-Subjects must be allocated , randomly , to
each of the treatment intervention .
c-Treatments are administrated in an
identical or controlled manner .
d-Treatment outcomes and other results
( side effect , costs , benefits ) must be
measured .
e-Statistical analysis is made to compare the
rates of measured treatment outcomes .
Strengths and limitations :
a-A clinical trial allows for control of
all variables ,which can also affect
outcomes under investigation .
b- An insufficient number of subjects
may lead to failure to detect true
differences .
META_ANALYSIS STUDY:

-Description:
 Meta- analysis seeks to combine the results of
several clinical studies on the same issue to
derive definite conclusion from the varied and
sometimes contradictory results.
 Similar to a review article, a meta- analysis
begins with a literature review identifying
studies of a similar research question.
 Unlike a review article, meta- analysis
attempts to analyze statistically the aggregate
results to drive a single integrated conclusion.
Study question:

Describe on the best clinical approach to a

problem based on several related studies

- Examples:

-Fibrinolytic therapy for acute myocardial

infarction.
-Postoperative irradiation in breast cancer
treatment.
-Steroid treatment of acute hepatitis.
 D-Methodology:
 Formulation of meta-analysis includes qualitative

and quantitative techniques.

-Qualitative aspects include:
 a-Developing the research question to be

analyzed.
 b-Reviewing the literature for relevant clinical

studies.
 c- Evaluating the studies to identify similarities or

to explain differences among them.

 d-Select the best clinical outcome.

-Quantitative aspects include:

 Statistical analysis of the results.
What type of study to
:chose depends on

 what is the research question/ objective

 Time available for study
 Resources available for the study
 Common/rare disease or production problem.
 Often there are multiple approaches which will
all work
 Choosing an established design gives you a
huge head start in design, analysis and
eliminating biases
Ethics of clinical
studies :
Definition

Ethics of clinical studies concern the

balance between risks and benefits
of individuals who participate as
subjects in research studies.
 Protection of human rights :

 Any person who is requested to consent

to participate as a subject in a research
study has the right to :
 Be informed of the nature and purpose of
the experiment .
-Be informed about the steps to be followed in
the experiment .
 Be informed of any attendant discomforts

and risks to be expected from the

experiment .
 Be given an explanation of any benefits to

the subject to be expected from the

experiment .
 Be informed of medical treatment to the
 Be given an opportunity to ask any
questions concerning the experiment or the
procedures involved .
 Be instructed that consent to participate in
the medical experiment may be withdrawn
at any time , and the subject may
discontinue participation in the experiment
without prejudice.
 Be given a copy of a signed and dated
written consent form when one is required
 Be given an opportunity to decide to
consent or not to consent to a medical
experiment without the intervention of any
element of force .
Problems
Problems 1:
 For each case history described
below, select the study design it
most appropriately illustrates.
 A-Case report
 B-Case- control study
 C-Clinical trial
 D-Cohort study
 F-Case series report
A
A total of 300 newly diagnosed
patients with laryngeal cancer are
allocated to treatment with either
surgical excision alone or surgical
excision plus radiation treatment.
B
 Patients admitted for carcinoma of
the stomach are age –and sex –
matched with fellow patients
without a diagnosis of cancer and
surveyed as to smoking history to
assess the possible association of
smoking and gastric cancer
c
-A 39 years old man who presents
with a mild fever, sore throat,
malaise, and headache is treated
with penicillin for presumed
streptococcal infection. He returns
after a week with hypotension,
fever, rash, and abdominal pain.
He responds favorably to
chloramphenicol, after a diagnosis
of Rocky Mountain spotted fever is
made.
d
A total of 3500 patients with thyroid
cancer are identified and surveyed
by patient interviews regarding
past exposure to radiation.
e
A total of 3000 elderly people living
in Tanta city were identified and
followed up for one year to
determine the frequency and risk
factors for falls among elderly
people.
Problem 2:
 In a prospective study, 500
children were followed up for 20
years to assess the risk for thyroid
cancer. 100 children were exposed
to radiation of neck ,and from this
group, 7 subjects developed
thyroid cancer. Also 3 subjects
developed thyroid cancer from the
non- exposed group.Calculate the
incidence rate(I R) and the relative
risk (R R) for thyroid cancer.
Problem 3
 In Pediatric Department Tanta
University, the staff decided to
determine the percentage of
medication compliance among
epileptic children attending the out
patient clinic for follow up and
obtain their medicine. How would
design a study to achieve this
objective?
Problem 4:
 There is evidence that lead
exposure has a significant effect
on children intellectual abilities
and academic performance. How
would you design a study to
examine this effect of lead on a
primary school children in Tanta
city?
Thank you