FACULTY OF MEDICINE

PRINCE OF SONGKLA UNIVERSITY

CLINICAL
TRIALS
EPIDEMIOLOGIC METHODS 2
NOVEMBER, 2023
OBJECTIVES
After completing this session, the students should be
able to…

•Describe the rationale for conducting a

clinical trial or an RCT
•Describe the steps in designing an RCT
•Describe the possible biases in
conducting a clinical trial
•Know how to register for a clinical trial
 CLINICAL TRIALS

Phases of drug Intervention

trials

Table Of RCT designs Hypothesis

Content Participants Control

Randomization Blinding
techniques

Clinical trial Protocol & Report

registry
 References
1. Cummings SR, Grady D, Hulley SB. Designing a Randomized Blinded Trial. In:
Hulley SB, Cummings SR, eds. Designing clinical research, 4th Ed. Philadelphia:
Lippincott Williams & Wilkins, 2013: 137-150.
2. Grady D, Cummings SR, Hulley SB. Alternative Clinical Trial Designs and
Implementation Issues. In: Hulley SB, Cummings SR, eds. Designing clinical
research, 4th Ed. Philadelphia: Lippincott Williams & Wilkins, 2013: 151-166.
3. Efird J. Blocked randomization with randomly selected block sizes. Int J Environ
Res Public Health. 2011;8(1):15-20. doi:10.3390/ijerph8010015
4. The CONSORT Statement:. Presentations are communication tools that can be
used as demonstrations, lectures, speeches, reports, and more. It is mostly
presented before an audience.
5. The SPIRIT Statement: Presentations are communication tools that can be used
as demonstrations, lectures, speeches, reports, and more. It is mostly presented
before an audience.
6. Kendall JM. Designing a research project: randomised controlled trials and their
principles. Emergency Medicine Journal 2003;20:164-168.
 CLINICAL TRIALS

Definition
A clinical trial is
any investigation in human subjects intended to
discover or verify the clinical, pharmacological,
pharmacodynamic effects of the product(s), the
effectiveness of medicine, surgery, radiotherapy,
education program with the object of ascertaining its
safety and/or efficacy.

https:// database.ich.org/sites/default/files/E6_R2_Addendum.pdf
 PHASES OF BIOMEDICAL TRIALS

Phase 1 Phase 2 Phase 3 IPhase 4

usually test new test treatments that are conducted on take place after
drugs for the first have been found to larger populations country approval
time in a small group be safe in phase I and in different and there is a
of people to evaluate but now need a regions and need for further
a safe dosage range larger group of countries, and are testing in a wide
and identify side human subjects to often the step right population over a
effects. monitor for any before a new longer timeframe.
adverse effects. treatment is
approved.
Randomized control trial
Treatment Follow-up

Randomization Compare results

Study population

Control Follow-up
DISCUSSION 1
Give an example of an RCT that you have ever
come across
Identify what are its
Participants
Intervention
Control
Outcome

Epidemiologic methods 2
Choosing intervention

EFFICACY SAFETY

BALANCE

DOSE, DURATION,
FREQUENCY PREVENTIVE
INTERVENTION CONDITION

TYPE OF
CURATIVE
TREATMENT
 FACULTY OF MEDICINE
PRINCE OF SONGKLA UNIVERSITY

Item 5 Item 1
20% 20%

RCT
designs Item 4
20%
Item 2
20%

Item 3
20%
 SINGLE GROUP
DESIGN

PARALLEL GROUP
DESIGN
PARALLEL GROUP
DESIGN

Tantirangsee N,
Assanangkornchai S, Marsden J.
Effects of a brief intervention for
substance use on tobacco
smoking and family relationship
functioning in schizophrenia and
related psychoses: a
randomised controlled trial. J
Subst Abuse Treat. 2015;51:30-
7.
CROSS-OVER DESIGN
 Cross-over design
Schwartz JA, Romeiser JL, Kimura R, Senzel L, Galanakis D, Halper D, Mena S, Bennett-Guerrero
E. Effect of chamomile intake on blood coagulation tests in healthy volunteers: a randomized,
placebo-controlled, crossover trial. Perioper Med (Lond). 2023 Sep 20;12(1):51.

Interventions: 7-day consumption of

chamomile tea (3 tea bags × 3 times daily
= 9 tea bags daily)
a chamomile extract capsule (3 times
daily)
a placebo capsule (3 times daily).
FACTORIAL DESIGN
Treatment A & Treatment B

R
A
N
D Treatment A & Placebo B
O TREATMENT TA PA
M
I
Z
A
T TB TA & TB PA & TB
I
O Placebo A & Treatment B
N

PB TA & PB PA & PB

Placebo A & Placebo B

Vitamin D and marine
omega 3 fatty acid
supplementation and
incident autoimmune
disease
 CLINICAL TRIAL

Withdrawal
design
Objectives
To assess response to the dose being
stopped or reduced.
To determine if treatment is still
required.
To discontinue participants in a study
that have not responded to the
medicine being studied. https://learning.eupati.eu/mod/book/view.php?
id=340&chapterid=259
CLINICAL TRIAL

R
A
TREATMENT A
N
D
O
M
I
Cluster
Z
A
randomized
T
I design
O
N TREATMENT B
Community-based type
2 diabetes care by lay
village health workers
in rural Lesotho

cluster-randomized trial

https://pubmed.ncbi.nlm.nih.gov/37875943/
 Low-income Mid-income High-income

Stratified
Youth Mid Senior Youth Mid Senior Youth Mid Senior randomized
11-34 35-64 >65 11-34 35-64 >65 11-34 35-64 >65 design

F M F M F M F M F M F M F M F M F M

R R R R R R R R R R R R R R R R R R
 -Non-inferiority +Non-inferiority

Hypothesis
Margin Margin

INFERIOR SUPERIOR
TREATMENT TREATMENT testing
EQUIVALENCE

Superior: a new therapy is

"better" than the established
standard treatment
SUPERIORITY

Equivalence: a new treatment is

STANDARD TREATMENT IS BETTER
neither worse or better than a
conventional treatment
NON-INFERIORIT
Non-inferior: a new treatment is
not inferior to a conventional
NEW TREATMENT IS BETTER
treatment
DIFFERENCE IN
EFFECT OF
TREATMENT
Participants
how to specify entry criteria defining a target population that is
appropriate to the research question and an accessible population
that is practical to study, how to design an efficient and scientific
approach to selecting participants, and how to recruit them

INCLUSION CRITERIA
EXCLUSION CRITERIA
SAMPLE SIZE
STRATIFICATION
INTERACTION
 CLINICAL TRIALS

Discussion
What are reasons for
excluding people from a
clinical trial?
 Reasons
for excluding people from a trial
1. A study treatment may be harmful.
Unacceptable risk of harm if assigned to active treatment
Unacceptable risk of harm if assigned to control
2. Active treatment is unlikely to be effective.
At low risk for the outcome
Has a type of disease that is not likely to respond to treatment
Taking a treatment that is likely to interfere with the
intervention
3. Unlikely to adhere to the intervention.
4. Unlikely to complete follow-up.
5. Practical problems with participating in the protocol.
 CLINICAL TRIALS

Types of controls in clinical trials

Placebo:
Compares experimental treatment(s) to a dosage form
without the experimental treatment.

Controls No-treatment:
Compares two groups, one of which does not receive the
experimental treatment.
Without a control group, the change
Dose-comparison:
may be due to alternative explanations:
Compares two or more active doses of the experimental
Predictable improvement
treatment.
Fluctuating disease severity
Active:
Hawthorn effect
Compares two or more experimental treatments.
Regression to the mean
Historical:
Practice effect
Compares observations in a study with results obtained in
an earlier study.
 CLINICAL TRIAL

Simple randomization
tossing a coin, random table, random by
calculator or computer
this technique may lead to substantial
differences in group size which will reduce
Randomization the precision of estimates of the
technique difference.
Block randomization
this technique randomizes n individuals
into k treatments, in blocks of size m.
this will ensure a close balance of the
numbers in each group.
 CLINICAL TRIAL

Block
randomization
CLINICAL TRIAL

Different block size

CLINICAL TRIAL
Unblind (open label):
Subject, investigator, and evaluator know the
treatment.
Single-blind:
Either the subject, investigator, or evaluator does not
know the treatment.
Double-blind:
Two of the parties (evaluator, subject, investigator) do
not know the treatment.
Triple blind:
Three of the parties (evaluator, subject, investigator) BLINDING

do not know the treatment.

Double-dummy:
A method used to enable blinding when two
treatments cannot be made identical in appearance
 THYNK UNLIMITED

Discussion
What are common
methodological
problems in RCT?
Clinical trial registry

http://www.clinicaltrials.in.th/index.php?
meun=home&smenu=home
Preparing a clinical trial protocol

http://www.spirit-statement.org/spirit-statement/
Reporting a trial

http://www.spirit-statement.org/spirit-statement/
 Flow diagram of RCT
(CONSORT statement)
 CLINICAL TRIALS

QUESTIONS