Clinical trial design
By
Izzatullah Khan
Assistant Professor
Pharm D (LCPS) MSc. Clinical Pharmacy
(UK)
Clinical Trials
Definition
“ Clinical trials are a set of procedure in medical
research and drug development that are conducted to
allow safety and efficacy data to be collected for
health interventions ( e.g., drugs, diagnostics, therapy
protocols)”
•Clinical trails are medical research studies in which
people enrolled as participant help to find out if a new
procedure is safe and effective.
Clinical Trial Design
•Clinical trial can generate the required
information about a new drug.
• Clinical trial could be designed in following
forms
Uncontrolled open trails
Controlled trails
Uncontrolled Trials.
It is the simplest design of a clinical trial.
In this both patient and investigator know which
treatment is being given
In this trial there is no comparison group.
The results are collected and studied and an inference
drawn in response.
It is also known as open trials.
Controlled or Comparative Trials.
In this trial two group of patient are participated.
One group is treated with new/investigational drug while
other group serves as control.
Controlled trial are of following type.
a) Parallel
b) Randomization
c) Blinding trial
d) Cross over trial
e) Latin square
f) Factorial design
g) Sequential design
a) Parallel Group Design
A parallel group study is a simple and
commonly used clinical design which compares
two treatments.
• Usually a test therapy is compared with a
standard therapy.
• The groups are typically named
the treatment group and the control group.
Parallel group designs do not require the same
number of subjects in each group.
Treatment Group Control Group
Exp. Drug
Advantage
a) It’s simple and easy to implement.
b) It is universally acceptable.
c) It is applicable to acute conditions.
d) Analysis is less complicated and
interpretation is straight forward.
Disadvantage
•It does not into account the inter-individual
variability.
b) Randomization
• A study in which participants assigned by
chance(not by the investigators’ choice) to their
particular group.
• A study in which a number of similar people are
randomly assigned to 2 (or more) groups to test a
specific drug or treatment.
•The groups are followed up to see how effective the
experimental treatment was. Outcomes are measured
at specific times and any difference in response
between the groups is assessed statistically.
• This method is also used to reduce bias.
The benefits of randomization are as follows:
•It eliminates selection bias .
• It eliminates confounding by adjusting for co-variates.
• It facilitates blinding of the identity of treatments from
investigators, participants, and assessors.
Advantages:
Easy to construct, can accommodate any number of
treatment and subjects, Simple to analyze.
Disadvantages:
•Although can be used for number of treatments, but suited
for few treatments.
•All subjects must be homogenous or random error will
occur.
c)Blinding Trials.
Blinding is defined as an experimental condition
in which various groups of the individuals
involved with the trial are withheld from the
knowledge of the treatments assigned to patients
and corresponding relevant information.
Blinding trials may be of two types:
1. Single Blinding Trial
2. Double Blinding Trial
1. Single –blind
A study in which the investigators know
which treatment each participant is receiving
but participant do not.
2. Double –blind
A study in which neither the participant nor
investigators who work with them knows
which treatment or placebo is being given to
which participant
d) Cross Over Trial.
A study in which participants are randomly assigned one of
two or more treatment options for specified time period.
When that time period ends, participants “cross over” to
one of the remaining treatment for another specified time
period.
Advantage
• Good precision, Economic, can be performed with few
subjects, useful in observing
• Effects of treatment over time in the same subject
•Disease in stable condition,e.g Migraine
Disadvantage
•Not useful for acute disease
•Assumes no period carry over
e)Latin Square Design
Latin square design each subject receives each treatment
during the experiment.
It is a two factor design ( Rows=Subjects and
Columns=Treatments ). Carry –over effects are balanced.
Advantages: minimize variability of plasma profiles and
carry-over effects. Small scale experiments can be carried
out for pilot studies. Possible to focus on formulation
variables.
Disadvantages: Less degree of freedom, randomization is
complex, long time study, more formulations more complex
study, subject dropout rates are high.
-With the Latin Square design we are able to control
variation in two directions.
-Treatments are arranged in rows and columns
Factorial Designs
Factorial designs allow for researchers to test multiple
interventions or treatment combinations in a single study.
Allows researchers to test individual treatment effects and/or
interactions between different treatments.
Uses:
1. Make efficient use of clinical trial subjects by evaluating
two treatments with same no. of individuals.
2. Influence of a number of factors can be studied together
which might require many trials if done individually.
3. Establish dose-response characteristics of the
combination of A and B when efficacy of each has been
previously established.
Advantages:
1. A greater precision can be obtained in estimating
the overall main factor effects.
2. Interaction between different factors can be
explored.
3. Additional factors can help to extend validity of
conclusions derived.
Disadvantages:
4. Difficult to analyse.
5. Large designs require large no of subjects.
6. Between subjects design lacks statistical power.
Sequential Design
•Here the participants are sequentially enrolled
in the study and are assigned a treatment
(usually at random).
•The efficiency, safety and efficacy of the
experiment is improved by changing the rules
as the study progresses.
Advantages
Reduces the needed no. of patients
Stops the trial when the aim can be answered
Can be combined with all kind of design
Disadvantages
Have to be statistically monitored during the
study
Need special data software
