In the name of Allah, the most

beneficent and merciful

Study Designs in Medical
Research
Dr Dilshad Ahmed Khan
MBBS,MCPS FCPS, FRC Path, MS, Ph.D
Professor of Pathology, NUMS Rawalpindi
 Sequence
 Introduction
 Types of study design
 Observational studies
 Analytical studies
 Intervention Studies
 Clinical trials
 Strengths & weaknesses of each designs
 Introduction
Medical Research
To acquire new knowledge to help,
prevent, detect, diagnose, and treat
disease from the rarest genetic
disorder to the common cold.
 Introduction
• Clinical research is important for producing
scientific evidence that influence the clinical
decision making in diagnosis & management of
the patient.
•Different types of research question may be
formulated depending on the existing gap in
the medical knowledge that require different
study designs.
 Medical Study Design

Study Design is based on

 Objectives of the study

 Resources available

 Time period for study

 Ethical considerations
 Types of Study Designs
• Observational Studies: Describe disease/ Health parameters

Descriptive studies

Analytical(comparative) studies
• Intervention Studies: Researcher intervene subjects to
produce therapeutic effect

Quasi-Experimental studies

True Experimental studies

Clinical trial
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Types of studies
 Descriptive Studies
Descriptive studies involve the
systematic collection of data to give a
clear picture of a particular: Social, economic,
politic and religious
factors

– Disease

– Health problems

– Situation & factors Agent Environment

Host
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 Case report/Case series
 Describe a single or multiple cases of a rare
disease

 Describe new disease/ findings/presentation

of the disorder

 Cannot draw conclusions regarding cause

and effect relationship
 Cross sectional Study
 Distribution of a disease

in the papulation /region

 Exposure & outcome are measured

simultaneously

 Provides a information of particular disease

(snapshot) of a population at given time
period.

 Hypothesis generating/health care planning

 Measure of Disease Burden

Incidence (new cases)) Recovery

Loss to follow-up

Prevalence (existing cases))

Deaths
Measure of Disease Burden

• Incidence • Prevalence

new cases old and new cases

I= —————————— P= —————————
population at risk population at risk

Calculated over a time period Calculated at a specific time (point

prevalence) or during a specified
(cumulative incidence)
time period (period) prevalence)
 Incidence = ?/N Prevalence = ?/N

Disease duration Observation

period
 Example :Cross-sectional Study
• Frequency/Prevalence / Incidence:

– How many para medical staff at PIMS

hospital are having HbsAg ?

– What is the age and sex distribution?

• Cross-sectional surveys:

National Health and Nutrition Survey

Study Design: Cross sectional
Advantages Disadvantages
• Low cost • Cannot prove correlation
• Simple • Survival bias

• Quick • Recall bias

• Ethically safe
 Analytical Studies
• Compare two or more groups, some of
which have developed the disease and
other not.
• An analytical study attempts to establish
causes or risk factors for certain diseases.

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 Design: Case Control Study
 Compares two groups whom a disease is

present (hepatocellular carcinoma) with a

control group where the disease is absent

 Find out association of risk factors that

have contributed to the disease.

 Design : Case-control Study
TIME
Direction of inquiry

Exposed Cases
(People with
Not exposed disease)
Population

Exposed Control
(People without
Not exposed disease)
 Example: Case Control
Cases Controls
LUNG CANCER FREE OF ILLNESS

EXPOSED NOT EXPOSED EXPOSED NOT EXPOSED

SMOKED NEVER SMOKED SMOKED NEVER SMOKED

Proportions of exposed to unexposed in cases and controls

 Odds Ratio (OR)
• Odds Ratio is a measure of association between
exposure and an outcome.
• Odd ratio = exposure of patients = Outcome > 1
exposure of control
• Derivation of OR is based on three assumptions:

- Disease must be relatively rare.

- Cases must be representative of the disease

- Controls must be representative of without disease

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Is HBV associated with hepatocellular Ca ?
HBsAg Hepatoma Control Total

Status

HBsAg +ve a=60 b=40 a + b=100

HBsAg -ve c=40 d= 60 c + d=100

Total 100 100 a+b+c+d

Find the odd ratio in the given scenario to interpret

the result .
• Odd ratio = a/c ÷ b/d
= a/c x d/b
= 60 x 60
40 x 40
= 2.25
• Interpretation:

• The patient with HBsAg have 2.25 time more

chance of developing hepatoma than control
 Case Control Design:
Advantages and Disadvantages

• Efficient /quick solution

• Etiology of long latency period

• Disease and exposure have already occurred

• Potential for bias remains

 Cohort Studies
• Selection of cohort/groups
A group of individuals that is exposed to a risk factor
(study group) is compared with a group of individuals
not exposed to the risk factor (control group).

• Conceptually longitudinal
The researcher follows both groups over time and find
out the relative risk (risk factors) of diseases in the

exposed group vs non-exposed group.

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 DESIGN OF COHORT STUDY

TIME
Direction of inquiry

Disease
Exposed
People Healthy
Population Without the
disease
Disease
Not
Exposed
Healthy
 Prospective Study
Defined population
NON-Randomized

EXPOSED NOT EXPOSED

2018 2018

2020 2020
DEVELOP DO NOT
DEVELOP DO NOT
DEVELOP
DISEASE DISEASE DEVELOP
DISEASE
DISEASE

Designs of a COHORT Study

 Relative Ratio/Risk
Not
exposed Incidence among
Non exposed

exposed
Incidence among
exposed

Ratio of incidence of the disease among exposed with non-exposed 28

Measure of the association between suspected cause and effect
 Measures of Associations
Relative risk (RR)

What does RR=1 means ?

RR = Incidence in exposed = 6
I Incidence in unexposed 2

what is expected RR of the case -------?

 cohort study design
• Advantages

– Ascertainment of natural history of disease

– Temporal sequence b/w cause & outcome

• Disadvantages

– Selection bias

– Loss to follow up

– Expensive
 Experimental Studies

• Experimental studies are ones where

researchers introduce an intervention and
study the effects on the subjects.

• One group is subjected to an intervention or

given the drug, while the other group not.

• Only type of study design that can actually

prove causation.
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Type of Experimental Studies
• True experimental Study design (RCT)

• Quasi – Experimental Studies Design

- -

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 True Experimental Study Design

The classical experimental study

design has three characteristics:

• Randomization

• Manipulation

• Control

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 Randomization
• It is the process by which participants have an
equal chance to be assigned to one of two or
more groups:

• One group gets the most standard

treatment/placebo

• The other groups gets the new treatment being

tested, which researchers have reason to
believe will be better than standard treatment
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 Defined population

Randomized

AHA Step-I diet

Normal diet

DEVELOP DO NOT
DEVELOP DO NOT
DISEASE DEVELOP
DISEASE DEVELOP
DISEASE
DISEASE

Randomization produces comparable groups &

reduces bias
 Quasi – Experimental Studies
• Quasi-experimental designs uses two (or more)
groups in which one of two conditions
(randomization or control) of true experimental
condition is missing.

• Employed when random assignment and

experimental control is impractical

• Ie Addition of pre- and post-treatment observations

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 Quasi – Experimental Studies

NON-Randomized

EXPOSED
NOT EXPOSED

DO NOT
DEVELOP DEVELOP DO NOT
DEVELOP
DISEASE DISEASE DEVELOP
DISEASE DISEASE
 Between Versus Within Designs
• Subjects are tested once: Between-Subjects Design.
• Subjects are used more than once or matched : Within-
Subjects Design
 Clinical Trials
• Clinical trials are medical or health-related
research done on human beings.

• A properly planned clinical trial is a powerful

experimental technique for assessing the
effectiveness of an intervention and find better
ways to prevent, diagnose, or treat diseases.

• Without them, we could not ensure safe &

effective treatments for the diseases.
 Types of Cancer Clinical Trials
• Treatment Trials - test new treatments, new
combination of drugs or new approaches to surgery
or radiation Treatment trials

• Screening Trials - test the best way to detect or

treat diseases

• Prevention Trials - look for better ways to prevent

diseases

• Diagnostic Trials - determine better tests or 40

Clinical Trials are Done in Phases:
• Preclinical trial – research on a new
drug or a new medical device or
procedure, usually done on
animals, to learn about
mechanisms of action, determine
how well the treatment works, and
see if it is safe to test on humans.
 Phase I Clinical Trial
• How does the agent affect the human body?

• What dosage is safe & identify side effects?

• Researchers test treatment in a small group

of healthy volunteers (approximately 20-40)
for the first time.
 Phase II Clinical Trial
• The experimental drug is administered to a larger
group of patients (approximately100-300) to
determine its effectiveness and to further evaluate
its safety.
 Phase III Clinical Trial
• The experimental drug or treatment is administered to
a large group of patients (300-3,000 or more) to
confirm its effectiveness, monitor side effects, and
compare it with standard or equivalent treatments.
 Phase IV Clinical Trial
After a drug is licensed (approved by the FDA)
or treatment is launched, researchers track its
safety, more information about a drug or
treatment’s risks, benefits, and optimal use or
any unexpected side effects occur in
individuals. 2010 2011
 Blind and Double Blind Trials
• A Blind Trial is a trial in which the patients
do not know if they are receiving the
treatment or a placebo.

• A Double Blind Trial is a trial in which the

patients and the researchers do not know
who is receiving the treatment.

• Why would the above be good ideas?

 Informed consent:
• Purpose

• Procedures

• Risks and potential benefits

• Ensure that risks are minimized

• Individual rights

• Ensure data integrity

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Past Present Future
Cross-sectional study
Exposure  Outcome

Case-control study
Exposure  Outcome

Prospective Cohort study

Exposure  Outcome

Experimental study/ RCT

Exposure

Outcome