Clinical Trial Design

Why Do a Clinical trial?

• To answer a clinical problem

• To gain a knowledge about a new or the
established treatment
• To support a “claim”
-for gaining government approval
-for marketing a drug, device or technique
 What is a clinical trial?
• A clinical trial is a tool for testing a drug,
device or technique
 How to design a clinical trial?
• Start with the hypothesis
• Then turn it into a specific question
- “Answerable”
- Basis for “Objectives”
• Design the details of intervention
• Choose the outcome you wish to measure
 Types of clinical Trial
One way of classifying clinical trials is by the way the
researchers behave.
• In an observational study, the investigators observe the
subjects and measure their outcomes. The researchers do
not actively manage the experiment. This is also called
a natural experiment
• In an interventional study, the investigators give the
research subjects a particular medicine or other
intervention. Usually, they compare the treated subjects to
subjects who receive no treatment or standard treatment.
Then the researchers measure how the subjects' health
changes.
Another way of classifying trials is by their purpose.
The U.S. National institutes of Health (NIH)
organizes trials into five (5) different type
• Prevention trials: look for better ways to prevent disease
in people who have never had the disease or to prevent a
disease from returning. These approaches may include
medicines, vitamins, vaccines, minerals, or lifestyle
changes.
• Screening trials: test the best way to detect certain
diseases or health conditions.
• Diagnostic trials: conducted to find better tests or
procedures for diagnosing a particular disease or condition.
• Treatment trials: test experimental treatments, new
combinations of drugs, or new approaches to surgery or
radiation therapy.
• Quality of life trials: explore ways to improve comfort
and the quality of life for individuals with a chronic illness
(a.k.a. Supportive Care trials).
 Parallel Design
Screen

Trt A
Randomize -
Trt B
• A parallel study is a type of clinical study where two
groups of treatments, A and B, are given so that one group
receives only A while another group receives only B.
• Other names for this type of study include "between
patient" and "non-crossover"
 Crossover trials
• Each participant gets both treatments being tested.
• Some participants are assigned at random to receive drug
A, and later, drug B. Others receive B, then A.
• To produce valid results, the effect of the first drug must
end before the second drug is taken, and vice-versa.
• A crossover design is a repeated
measurements design such that each experimental unit
(patient) receives different treatments during the different
time periods, i.e., the patients cross over from one
treatment to another during the course of the trial.
 Factorial design
• Factorial clinical trials test the effect of two or more
treatments simultaneously using various combinations of
the treatments.
• The simplest factorial design is known as a 2x2 factorial
design, whereby participants are randomly allocated to one
of four combinations of two interventions (A and B, say).
• These combinations are A alone, B alone, both A and B;
neither A nor B (control).
• This design allows the investigators to compare the
experimental interventions with the control, compare the
experimental interventions with each other, and investigate
possible interactions between them (that is, comparison of
the sum of the effects of A and B given separately with the
effects of the combination).
 Purpose of control group
• To allow discrimination of patient outcomes
caused by experimental intervention from
those caused by other factors
 Types of Control Group
• External
– Historical
– Concurrent
• Internal
– Placebo
– Active (Positive) control
• Multiple
– Both an Active and Placebo
Clinical Trials Greatest Enemy

• BIAS
 How do we minimize bias?

• Equivalent Groups
• Standardized Outcome
• Randomization
• Blinding
• Blinded, randomized trials
-Randomized means people are assigned at
random either to receive the new drug, the
standard treatment for that disease, or a
nonfunctional substitute
-Many Phase III trials are randomized, double-
blind trials.
• Open trials
-Not every trial is blind.
-In unblinded trials, often described as open trials, both
doctors and participants know what treatments are being
given.
-Trials of surgical procedures and comparisons of medical
devices
Disadvantages:
Many participants may not want to take placebos
 Blinding
• No Blind
– All patients know treatment
• Single Blind
– Patient does not know treatment
• Double Blind
– Neither patient nor health care provider know treatment
• Triple Blind
– Patient, physician and statistician/monitors do not know
treatment
 Double Dummy Design
• Double dummy is a technique for retaining the blind when
administering supplies in a clinical trial, when the two
treatments cannot be made identical.
• Supplies are prepared for Treatment A (active and
indistinguishable placebo) and for Treatment B (active and
indistinguishable placebo). Subjects then take two sets of
treatment; either A (active) and B (placebo), or A
(placebo) and B (active).
• Double dummy is a method of blinding where both
treatment groups may receive placebo.
 Double Dummy Design
• For example, one group may receive
Treatment A and the placebo of Treatment
B; the other group would receive Treatment
B and the placebo of Treatment A.
 Matched pair trial design

• In the matched-pair design, participants are first

matched in pairs according to certain
characteristics.
• Then, each member of a pair is randomly assigned
to one of the two different study subgroups.
• This allows comparison between similar study
participants who undergo different study
procedures.
•
 Matched pair trial design

After screening, participants are matched into pairs. Within each pair, one participant
is randomised onto Treatment A while the other is randomised onto Treatment B.
 Withdrawal trials
• In a withdrawal trial, the participant
receives a test treatment for a specified time
and are then randomised to continue either
with the test treatment or a
placebo (withdrawal of active therapy).
 Withdrawal trials

During a withdrawal trial, after the first specified period of time has elapsed,
participants are randomised into two groups, one of which receives a placebo
instead of continuing to receive the active treatment.
 Adaptive Clinical Trial
• Adaptive / flexible trial design has
begun to catch-up with the clinical trial
services providers
• The idea of adaptive trial design was
initiated in late 1970s
What Is Adaptive Clinical Trial?
• An adaptive design is a clinical trial
design that allows the users to adapt or
modify a trial during its progress based
on interim results without affecting the
validity and integrity of the trial. These
adaptations can be based on internal or
external information to the trial.
• Interim Analysis
All adaptive designs include interim
analyses. An interim analysis is a
statistical analysis conducted during on-
going trial based on trial data. The
purpose of interim analysis is to
determine whether the trial should stop
early or continue to further collect data
or make modifications.
Thank You