International Journal of Trend in Scientific Research and Development (IJTSRD)

Volume 7 Issue 2, March-April 2023 Available Online: www.ijtsrd.com e-ISSN: 2456 – 6470

Randomized Clinical Trial

Atika Siddiqua1, Hiba Ahmed2, P. Aravind3
1
Pharm D, Student at ClinoSol Research, Hyderabad, Telangana, India
2
M. Pharmacy, Student at ClinoSol Research, Hyderabad, Telangana, India
3
B. Pharmacy, Student at ClinoSol Research, Hyderabad, Telangana, India

ABSTRACT How to cite this paper: Atika Siddiqua |

Randomized controlled trials (RCTs) are widely used in medical Hiba Ahmed | P. Aravind "Randomized
research to assess the effectiveness of medical interventions. RCTs Clinical Trial"
are designed to reduce the potential for bias and increase the Published in
International Journal
reliability of results by randomly assigning participants to either the
of Trend in
treatment group or the control group. In an RCT, the treatment group
Scientific Research
receives the experimental intervention, while the control group and Development
receives either no intervention or the standard treatment. By (ijtsrd), ISSN: 2456- IJTSRD55088
comparing the outcomes of the two groups, researchers can 6470, Volume-7 |
determine whether the intervention is effective, less effective, or no Issue-2, April 2023, pp.607-611, URL:
different in effectiveness. There are various types of RCT designs, www.ijtsrd.com/papers/ijtsrd55088.pdf
including simple RCT, cluster RCT, and factorial design. Blinding is
a technique used to reduce bias in RCTs. The results of RCTs are Copyright © 2023 by author (s) and
widely used to inform clinical practice, health policy, and decision- International Journal of Trend in
making. Scientific Research and Development
Journal. This is an
KEYWORDS: Randomized controlled trials, Clinical trials, Medical Open Access article
research, Intervention, Treatment efficacy distributed under the
terms of the Creative Commons
Attribution License (CC BY 4.0)
(http://creativecommons.org/licenses/by/4.0)

INTRODUCTION
Randomized clinical trial or randomized controlled
trial (RCT) is a trial in which subjects are randomly
assigned to one of two groups: the experimental
group or treatment group and the comparison group
or control group.1,2,3 The experimental group is the
group receiving the intervention or the drug being
tested. The control group is the group receiving the
standard or conventional treatment. The two groups
are then followed up to determine the differences
between their outcomes.3,4 The results and subsequent
analysis of the trial are used to assess the
effectiveness of the intervention, that is the extent to
which a treatment, procedure, medical device or
service benefits the patients.5,6
Randomized clinical trials (RCTs) are a type of
scientific experiment that are widely used in medical
research to assess the effectiveness of medical
interventions.7 They are designed to reduce the
potential for bias and increase the reliability of the
results by randomly assigning participants to either
the treatment group or the control group.8 This
random assignment helps to ensure that any
differences in the outcomes between the two groups
are due to the intervention being tested, rather than
any pre-existing differences between the participants.9
In an RCT, the treatment group receives the
experimental intervention, which could be a new
drug, a medical device, a surgical procedure, a
behavioral intervention, or a public health
intervention, depending on the research question
being investigated. The control group, on the other
hand, receives either no intervention or the standard
or conventional treatment that is currently available
for the condition being studied. By comparing the
outcomes of the two groups, researchers can
determine whether the experimental intervention is
more effective than the standard treatment, less
effective, or no different in effectiveness.10
After the participants have been randomly assigned to
either the treatment group or the control group, they
are followed up over a defined period of time to
determine the differences between their outcomes.
The outcomes that are measured can vary depending
on the research question being investigated, but they
often include measures such as survival rates,

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symptom relief, quality of life, and adverse effects of
the intervention.8,9,10
The results of the trial are then analyzed to determine
the effectiveness of the intervention being tested. This
analysis can involve statistical methods to compare
the outcomes of the treatment group and the control
group, and to determine the likelihood that any
observed differences between the groups are due to
chance or are actually a result of the intervention
being tested. Once the results have been analyzed,
they are often published in peer-reviewed scientific
journals and can be used to inform clinical practice
guidelines, regulatory decisions, and insurance
coverage decisions.10
Overall, randomized clinical trials are considered the
gold standard for evaluating the effectiveness of
medical interventions, as they are designed to
minimize the risk of bias and increase the reliability
of the results. While they are not without limitations,
RCTs remain an essential tool for improving patient
care and advancing medical knowledge.
Types of Randomized Controlled Trials:
1. Simple RCT design:
A simple RCT design has only one treatment group
and one control group. Participants are randomly
assigned to either the treatment group, where they
receive the experimental intervention, or the control
group, where they receive either no intervention or
the standard treatment. The outcomes of the two
groups are then compared to determine whether the
intervention is effective. This design is typically used
when there is only one intervention being tested and
there is no need to compare different types of
interventions.11
2. Cluster RCT design:
In a cluster RCT design, participants are randomized
into groups or "clusters" rather than as individuals.
These clusters could be schools, communities,
hospitals, or any other group that is relevant to the
research question. Each cluster is then randomly
assigned to either the treatment group or the control
group. This design is often used when the
intervention being tested is not possible to deliver to
individuals and is better suited for delivery at the
group level. For example, a public health intervention
aimed at reducing smoking rates may be delivered to
entire communities rather than individual
participants.12
Within the cluster RCT design, there can be multiple
treatment groups and a control group. For example,
the first treatment group could receive Intervention -
A, the second treatment group could receive
Intervention - B, and so on. This allows researchers to
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compare the effectiveness of different interventions
and determine which one works best.13
3. Factorial design:
In a factorial design, there are two or more
interventions being tested simultaneously.
Participants are randomly assigned to one of four
groups: the first group receives Intervention - A only,
the second group receives Intervention - B only, the
third group receives both Intervention - A and B, and
the fourth group receives no intervention or the
standard treatment.
This design allows researchers to test the
effectiveness of each intervention individually and in
combination with each other. For example, if
Intervention - A is a new medication and Intervention
- B is a dietary change, the factorial design would
allow researchers to determine the effectiveness of
each intervention on its own as well as the
effectiveness of the two interventions combined.14
The choice of RCT design depends on the research
question being asked and the intervention being
tested. Researchers carefully consider the advantages
and disadvantages of each design before selecting the
most appropriate one for their study.11-15
Advantages of Randomized controlled trials:
Randomized controlled trials (RCTs) have several
advantages that make them one of the most rigorous
designs for testing the efficacy of a treatment or
intervention. Here are some detailed explanations of
the advantages of RCTs:
Most convincing design:
RCTs are considered the most convincing design for
determining the effectiveness of an intervention
because they use randomization to ensure that
participants are assigned to the treatment and control
groups without any bias. This eliminates the
possibility that any observed differences between the
two groups are due to chance or some other factor,
and increases the confidence in the results.4,5,6
Only design which controls for unknown or
unmeasurable confounders:
Randomization in RCTs also ensures that any
unknown or unmeasurable confounding variables are
distributed evenly between the treatment and control
groups. This means that the effect of the intervention
can be attributed to the intervention itself, rather than
to some other factor that may be influencing the
outcome.7.8
Good randomization can eliminate any
population bias:
Good randomization techniques ensure that the study
population is representative of the larger population
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being studied. This means that any observed effect of
the intervention can be generalized to the larger
population with greater confidence.4
They are easier to blind / mask than
observational studies:
RCTs are often designed to be double-blind, where
neither the participant nor the researcher knows
which group the participant has been assigned to.
This reduces the risk of bias in the study, as both the
participant and researcher are less likely to be
influenced by their expectations or beliefs about the
intervention.6
The results can be analyzed with familiar
statistical tools:
RCTs are designed to be highly controlled and
standardized, which makes the results easier to
analyze using well-established statistical techniques.
This makes it easier to compare the results of
different RCTs and to draw conclusions about the
effectiveness of the intervention being studied.8
The populations of participating individuals
are clearly identified:
In RCTs, participants are clearly identified and their
characteristics are well-defined. This makes it easier
to determine the generalizability of the results to other
populations and to understand which populations may
benefit most from the intervention.
Randomized controlled trials are considered one of
the most rigorous designs for testing the efficacy of
interventions. Their advantages include the ability to
control for confounding variables, eliminate bias, and
the ability to generalize results to larger populations.
Additionally, RCTs are often designed to be double-
blind, making them less susceptible to bias and easier
to analyze statistically.12
Disadvantages of Randomized controlled trials:
Randomized controlled trials (RCTs) are considered
the gold standard for evaluating the efficacy of
treatments or interventions. However, they also have
some disadvantages that should be considered when
evaluating their use. Here are some detailed
explanations of the disadvantages of RCTs:
Most expensive in terms of time and money:
RCTs are often the most expensive type of clinical
study to conduct, due to the need for a large sample
size, strict inclusion criteria, and long follow-up
periods. The cost of conducting RCTs can limit their
feasibility and availability.12
Artificial:
RCTs are often conducted under highly controlled
conditions, which may not reflect real-world clinical
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practice. This artificial environment can limit the
generalizability of the results to a broader
population.2
Ethical objections:
RCTs require that some participants receive a placebo
or no treatment, which can raise ethical concerns
about withholding treatment from patients.
Additionally, RCTs may expose participants to
unnecessary risks, which can also raise ethical
concerns.5
The population involved is selected, so it can be
different from real clinical practice and may
not be representative of the whole:
RCTs often use a highly selected population, which
can limit the generalizability of the results to the
broader population. This may result in treatments
being developed that work well in a specific
population but are not effective in the general
population.4
They cannot be generalized or compared to a
general practice setting:
RCTs are often conducted under highly controlled
conditions, which may not reflect real-world clinical
practice. This can limit the ability to generalize the
results to a broader population or to compare the
results to a general practice setting.2
There may be a loss to follow-up attributed to
treatment:
Participants in RCTs may not complete the study due
to the side effects of the treatment or other reasons.
This loss to follow-up can affect the reliability of the
results and reduce the sample size, which can limit
the statistical power of the study.5
Randomization:
In experiments having more than one treatment,
subjects are assigned to either of the treatment
groups. In the absence of guidelines on allocation of
subjects, 50% of the subjects may be assigned to one
treatment group and the rest 50% of the subjects may
be assigned to the other treatment group. This process
of allocation of subjects is likely to create bias and
imbalance of some factors resulting to an unrealistic
conclusion. Hence, the subjects should be randomly
assigned to treatment groups. In random assignment,
the probability of each subject to either of the
treatment groups is equal. No one can predict in
advance the treatment group to which the subjects
will get assigned. These random assignments are
consistent with the laws of probability. The first step
in randomized controlled trials is to identify subjects
that satisfy the selection criteria (inclusion/exclusion
criteria) as specified in the protocol.16-18
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Randomization techniques:
In randomization, the subjects are assigned to
different treatment groups using random tables
generated using the following appropriate
randomization techniques.
1. Simple Randomization:
In a simple randomization technique, the subjects are
assigned to one of the two treatment groups using
random tables or advanced computerized
techniques.16-18
2. Stratified Randomization:
Stratified randomization is used when the researcher
is interested to compare the subjects which can be
classified in to two groups, called as strata. Then the
subjects are then randomly assigned to either of the
two treatment groups, using a valid randomization
schedule. For example, an experiment in which the
subjects can be classified or stratified on the basis of
gender to males and females. 16-18
3. Factorial (balanced) Randomization:
Factorial randomization is used when the researcher
is interested to compare the subjects which can be
classified into different groups based on two or more
factors. For example, an experiment to compare the
treatment in depressed and non-depressed male and
female subjects. 16-18
It involves the following steps:
Identify the subjects satisfying the selection
criteria
Classify subjects based on the factor of sex as
males and females
Further classify subjects based on the factor
disease stares as depressed and non-depressed
Randomized subjects from each type (male
depressed, male non-depressed, female depressed,
female non-depressed) into treatment groups
using a designed randomization schedule. 16-18
Blinding:
In experiments where the researcher or investigator is
aware of what treatment is given to what subject there
is a likelihood of bias while assessment of the
response by the investigator. For example, there are
two treatments where one treatment is well-
established and the other is relatively new. The
investigator while recording responses may get biased
towards the well-established treatment. Similarly, the
subjects receiving the well-established treatment may
feel better psychologically. Blinding is a technique
used to reduce such biases.
Blinding refers to the process of concealing
information about the treatment or intervention from
one or more parties involved in a study. The purpose
of blinding is to reduce bias that may affect the study
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results and to improve the quality of the evidence
generated by the study.19,20
Open studies:
Open studies are also known as non-blinded studies.
In these studies, both the investigator and the
participants are aware of the treatments they are
receiving. Open studies are commonly used in studies
where blinding is not possible or practical.
Single-blind studies:
Single-blind studies are studies in which only one
party, either the investigator or the participants, is
aware of the treatment assignments. For example, in a
single-blind drug trial, the investigator may be aware
of the treatment assignments, but the participants may
not know which group they are in.
Double-blind studies:
Double-blind studies are studies in which both the
investigator and the participants are unaware of the
treatment assignments. This is considered the gold
standard for clinical trials because it helps to reduce
bias in the study results. Double-blind studies are
commonly used in drug trials and other clinical trials.
19,20
Triple-blind studies:
Triple-blind studies are studies in which the
investigator, the participants, and a third party, such
as a statistician or laboratory technician, are all
unaware of the treatment assignments. This type of
blinding is not commonly used, but it may be
employed in studies where there is a high risk of bias
or where blinding is particularly important.
Overall, the level of blinding used in a study depends
on the specific research question and the design of the
study. The goal is to choose the appropriate level of
blinding that will minimize bias and maximize the
quality of the evidence generated by the study. 19,20
Conclusion
Randomized controlled trials (RCTs) are considered
the gold standard in clinical research as they provide
the most convincing evidence on the effectiveness of
medical interventions. RCTs involve randomly
assigning subjects to either an experimental group
receiving the intervention or a control group receiving
standard treatment and then comparing their
outcomes. The use of randomization helps to
minimize bias and confounding variables, making the
results of the study more reliable. However, RCTs
also have some limitations, including being expensive
and time-consuming to conduct, and the ethical
considerations surrounding the use of a control group.
Additionally, RCTs may not always be representative
of real-world clinical practice, and there may be a loss
to follow-up attributed to treatment.
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Overall, RCTs are a valuable tool in clinical research
and continue to play a critical role in improving
healthcare outcomes. Properly designed and executed
RCTs provide the best evidence for the effectiveness
of medical interventions, leading to better healthcare
decision-making and ultimately, improved patient
outcomes.
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