Chapter 7

Experimental Study Design

Course Instructors
Dr.Ahmad Alhaykan Dr.Rayan Siraj
Dr.Sheeba Shaf Mr.Anton Alban
EXPERIMENTAL STUDY
DESIGN
TOPIC OUTLINE

Sub-types of Experimental
Study Designs
Randomized Controlled Trial
Field Trial
Community Trial
OBJECTIVES
At the end of this session, students will be able to:
Describe and Describe and explain the distinguishing features of experimental
studies, including randomized controlled trial, field trial and
explain community trial.

Describe and Describe and identify the types of epidemiologic questions that can
identify be addressed by experimental studies

Identify the strengths and limitations of randomized controlled trial,

Identify field trial and community trial
 Epidemiological Studies

Experimental
Observational
(Intervention)

Descriptive Analytical Randomized Controlled Trial

(Clinical Trial)

Cross-sectional Cohort
(Prevalence) (Prospective/Follow up)
Field Trial
Ecological
(Correlational) Case-control
(Retrospective)
Community Trial
Case series (Community Intervention
Study)
EXPERIMENTAL
STUDY DESIGNS
Intervention or experimentation involves attempting to
change a variable in one or more groups of people.
DEFINITION

• Researcher selects a number of people who are

similar in some characteristics so that the effect
of confounding is minimized
• Researcher randomly selects and divides these
people into subgroups (experimental and control
groups)
DEFINITION

• The experimental group is given a risk

factor for a disease
• Both groups are observed for the
development of the disease
DEFINITION

• Study subjects are enrolled on the

basis of their exposure, BUT the
exposure is allocated by the
investigator!!
• Also known as INTERVENTION
STUDIES
 PURPOSES

1 2 3 4
Evaluating new Evaluating Assessing new Assessing new
drugs/treatmen different programs for ways of
ts dosages of same screening and organizing and
drug early detection delivering
health services
TYPES

Randomized controlled trials

Field Trials

Community Trials
RANDOMIZED CONTROLLED
TRIALS (RCT)
DEFINITION

• Experiment in which individuals are randomly

allocated to receive or not receive an
• experimental diagnostic,
• preventive,
• therapeutic,
• or palliative procedure
and then followed to determine the effect of the
intervention
 RCT DEFINITION

• Subjects in the study population are randomly

allocated to intervention and control groups, and
the results are assessed by comparing outcomes.
• Also known as CLINICAL TRIALS
 PHASES OF CLINICAL TRIAL

Phase I Phase II Phase III Phase IV

• First in testing • 30-100 • 100+ patients • Post-

new patients • Efficacy and marketing
intervention • Preliminary safety • Observational
in human safety, safety, • Usually /controlled
• 10-30 healthy efficacy controlled trial
people • Effectiveness,
• Identify dose, side effects
drug
metabolism
RCT
RCT ADVANTAGES
•Provide strong evidence for the testing of
hypotheses
•The only method to test the effect of a new drug
or procedure
•Good randomization will "wash out" any
population bias
•Easier to blind/mask than observational studies
•Results can be analyzed with well known
statistical tools
•Populations of participating individuals are
clearly identified
RCT DISADVANTAGES
•Need approval from ethical committee
•human rights
•Difficult to conduct
•confounding bias (effects of differences among
subjects) / systematic bias (result different from the
truth)
•Volunteer biases:
•the population that participates may not be
representative of the whole
•Expensive
•Loss to follow-up attributed to treatment
DESIGNS OF RCT

• Parallel design
• most commonly used in the
experimental studies
• Cross-over design
• Group Allocation (Clustered)
• Factorial design
PARALLEL DESIGN

• Treatment & control

group
• Each person is
randomly assigned
to one treatment
group
• Randomization:
reduce treatment
selection bias
 CROSS-OVER DESIGN
• When a patient crosses from one treatment group
to another:
Unplanned crossover: Planned crossover:

• Patient changes his/her mind • Patients are randomly allocated into

• His/her own conditions worsens one treatment group, observed for a
• shifts to another treatment period of time, then shifted to
another treatment group
• Patient serves as his/her own control
• Be careful for washout period: no
residue carried out from first
treatment

• Cross-over endangers randomization when it increases

• Needs to be accounted for in results analysis
CROSS-OVER DESIGN
CROSS-OVER DESIGN -
DISADVANTAGE

• Treatment cannot have permanent effect

• Potential “carry-over” effect
• Need for “washout” period
• Dropouts are more significant
• Analysis may be more difficult
GROUP ALLOCATION DESIGN

• “Cluster” design
• Unit of randomization = “Group of
patients” (Community, hospital, school)
• Use when individual randomization is not
feasible ex. contamination
GROUP ALLOCATION DESIGN
 HYPOTHESIS OF TRIAL

SUPERIORITY EQUIVALENCE NON-INFERIORITY

TRIAL TRIAL TRIAL
 EQUIVALENCE TRIAL
• Objective: Show that intervention response falls
sufficiently close to control group response
• “Detectable difference”
• Null Hypothesis (H0)
• There is a difference between treatments
•A≠B
• Alternate Hypothesis (HA)
• There is no difference between treatments
• A=B
 NON-INFERIORITY TRIAL

• Objective: determine if the treatment is at least as good

as standard treatment
• Null Hypothesis (H0)
• Treatment A is worse than treatment B
•A<B
• Alternate Hypothesis (HA)
• Treatment A is equal to or superior to treatment B
•A≥B
 NON-INFERIORITY TRIAL

• Hypothesis of non-inferiority is one-sided

• Sample size is smaller than equivalency trial
 OUTCOMES IN RCT

Types

• Primary Outcome
• Secondary Outcome

Measurement of Outcome

• Dichotomous
• Time-to-event
• Rates
• Composite Measures
PRIMARY OUTCOME
• Reflects primary objective, primary
hypothesis
• “Design” variable
• Sample size is based on this outcome
• Should be relevant and likely to be
influenced by treatment
• Measurement should be accurate and
reliable
• Evaluation in all participants
SECONDARY OUTCOME

OTHER IMPORTANT SAFETY IN-BETWEEN

POTENTIAL EFFECTS MECHANISM OF EFFECT
OUTCOME MEASUREMENT
DICHOTOMOUS TIME-TO-EVENT
OUTCOME OUTCOME
• Yes or No • Dimension of time in
• Disease or No disease addition to
• Cutoff value for dichotomous outcome
continuous • Ex: time to death, time
measurement to hospital discharge
• Allow for censoring
(some patient loss
follow up)
 OUTCOME MEASUREMENT

COMPOSITE CONTINUOUS
RATES
MEASUREMENT VARIABLE
• Dichotomous, • Two or more • Value or
but allow events related changes from
repeated to disease baseline
outcome process • Typically more
powerful than
discrete
outcome
EFFICACY VS EFFECTIVENESS

Efficacy: in ideal
condition/best circumstance

Effectiveness: in real
situation
 EFFICACY VS EFFECTIVENESS EXAMPLE
• Asthma trial
• Efficacy measurement: Forced Expiration
Volume 1 (FEV1)
• Effectiveness measurement: hospitalization
rate
• Vaccine trial
• Efficacy measurement: Confirmed cases of
dengue infection with virological studies
• Effectiveness measurement: Clinical cases
Among the following, which are
examples of the RCT Designs?
A. Parallel Design
B. Cross-Over Design
C. Group Allocation Design
D. Factorial Design
E. All the above
Among the following, which are
examples of the RCT Designs?
A. Parallel Design
B. Cross-Over Design
C. Group Allocation Design
D. Factorial Design
E. All the above
Randomized Controlled Trial is also
known as:
A. Phase Trials
B. Field Trials
C. Clinical Trials
D. Community Trials
Randomized Controlled Trial is also
known as:
A. Phase Trials
B. Field Trials
C. Clinical Trials
D. Community Trials
Which of the following is an example
of TIME-TO-EVENT OUTCOME
MEASUREMENT?

A. Male or Female
B. Time to heart attack
C. Height Measurement
D. Rate index
Which of the following is an example
of TIME-TO-EVENT OUTCOME
MEASUREMENT?

A. Male or Female
B. Time to heart attack
C. Height Measurement
D. Rate index
Which of the following is an example
of DICHOTOMOUS OUTCOME
MEASUREMENT?

A. Male or Female
B. Time to heart attack
C. Height Measurement
D. Rate index
Which of the following is an example
of DICHOTOMOUS OUTCOME
MEASUREMENT?

A. Male or Female
B. Time to heart attack
C. Height Measurement
D. Rate index
Which of the following is an example
of CONTINOUS VARIABLE OUTCOME
MEASUREMENT?

A. Male or Female
B. Time to heart attack
C. Height Measurement
D. Rate index
Which of the following is an example
of CONTINOUS VARIABLE OUTCOME
MEASUREMENT?

A. Male or Female
B. Time to heart attack
C. Height Measurement
D. Rate index
A study in which participants are
randomly assigned to groups in which
one receives an experimental
treatment, and the second is similarly
treated, but is given a placebo, is
referred to as?
A. Randomly conducted treatment
B. Randomized control trial
C. Randomly conducted trial
D. None of the above
A study in which participants are
randomly assigned to groups in which
one receives an experimental
treatment, and the second is similarly
treated, but is given a placebo, is
referred to as?
A. Randomly conducted treatment
B. Randomized control trial
C. Randomly conducted trial
D. None of the above
Resources

• Bonita, R., R. Beaglehole,and T. Kjellström. (2006). Basic

Epidemiology 2nd edition. Geneva: World Health Organization. ISBN
9789241547079
• Aschengrau, A. and Seage, G. R. III (2014). Essentials of
Epidemiology in Public Health (3rd Edition). Burlington, MA: Jones
and Bartlett Learning. ISBN-13: 978-1-4496-5733-8

• Friis, R.H. and Sellers, T.A. (2014). Epidemiology for Public Health
Practice (5th Edition). Burlington, MA: Jones & Bartlett Learning.
ISBN-13: 978-1-4496-6549-4
THANK YOU FOR
LISTENING