RANDOMIZED CLINICAL TRIAL
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. 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. 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.
Figure - 1. Randomized Controlled Trials
Types of Randomized Controlled Trials:
Simple RCT design:
A simple RCT design have only one treatment group and a control group.
Cluster RCT design:
A cluster RCT design have multiple treatment groups and a control group. For example, first treatment group receives Intervention - A, second treatment group receives Intervention - B, and so on.
Factorial design:
In a factorial deign, one of the treatment groups receives a combination of Intervention - A or B.
Advantages of Randomized controlled trials:
Most convincing design
Only design which controls for unknown or unmeasurable confounders
Good randomization can eliminate any population bias
They are easier to blind / mask than observational studies
The results can be analyzed with familiar statistical tools
The populations of participating individuals are clearly identified
Disadvantages of Randomized controlled trials:
Most expensive in terms of time and money
Artificial
Ethical objections
The population involved is selected, so it can be different from real clinical practice and may not be representative of the whole
They cannot be generalized or compared to a general practice setting.
There may be a loss to follow-up attributed to treatment.
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.
Randomization techniques:
In randomization, the subjects are assigned to different treatment groups using random tables generated using the following appropriate randomization techniques.
Simple Randomization:
In simple randomization technique, the subjects are assigned to one of the two treatment groups using random tables or advanced computerized techniques.
Figure - 2. Simple Randomization
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.
Figure - 3. Stratified Randomization
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.
It involves 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
Figure - 4. Factorial Randomization
Blinding:
In the 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.
Figure - 5. Blinding techniques
Classification of studies on the basis of blinding:
Studies are classified into the following types based on the status of blinding.
Open studies:
Open studies are studies without blinding. The investigator and subjects are aware of the treatments.
Single Blind studies:
In single blind studies, one party either the investigator or subjects is aware of the assigned treatments.
Double Blind studies:
In double blind studies neither the investigator nor the subjects are aware of the treatments.
Triple Blind studies:
In triple blind studies, in addition to the investigator and the subjects, the statistician or the laboratory technician is also unaware of the treatments.
References:
Kendall JM. Designing a research project: randomised controlled trials and their principles Emergency Medicine Journal 2003; 20:164-168.
https://www.bioclever.com/randomized-clinical-trials-n-41-en
SK Gupta, Basic Principles of Clinical Research and Methodology, New Delhi: Jaypee Brothers Medical Publishers Pvt. Limited; 2007, Pg. 242-246
Student Name: Atika Siddiqua
Student ID: 011/012023
Qualification: PharmD
e-Mail ID: atika.sid5@gmail.com
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