definition types and methods included

1. RANDOMIZED CONTROLLED TRIAL
DHANADHARANI VENKATESH

2. RAMDOMIZED CONTROLLED TRIAL
The randomized controlled trial is considered as the most rigorous
method of determining whether a cause effective relationship exists between
an intervention and outcome
The strength of the RTC lies in the process of randomisation that is
unique to this type of epidemiological study design
Generally, in a randomised controlled trial, study participants are
randomly assigned to one of the two groups: The experimental group receiving
interventions that is being tested and comparison group (control) which
receives a conventional treatment or placebo
These groups are then followed prospectively to assess the effectiveness
of the intervention compared with standard or placebo treatment

3. RANDOMISATION
The aim of randomisation is to ensure that any observed difference between
the treatment groups are due to difference in the treatment alone and not due to
effects of confounding (known or unknown) or trials. That is ,the groups are
similar in all respects with the exception of the intervention under investigation
Method of random allocation are used to ensure that all study participants
have the same chance of allocation to the treatment or control group, and that
the likelihood of receiving an intervention is equal regardless of when the
participants entered the study.
Therefore, the probability of any participant receiving the intervention or the
standard treatment / placebo is independent of any other participant being
assigned that treatment

4. CRITERIA FOR RANDOMIZATION
Unpredictability
• Each participant has the same chance of receiving any of the
interventions.
• Allocation is carried out using a chance mechanism so that neither
the participant nor the investigator will know in advance which
will be assigned.
Balance
• Treatment groups are of a similar size & constitution, groups are
alike in all important aspects and only differ in the intervention
each group receives
Simplicity
• Easy for investigator/staff to implement

5. METHOD OF RANDOMISATION
Based on allocation of subjects to intervention and control group
1. Simple randomisation
2. Block randomisation
3. Stratified randomisation
4. Unequal randomisation
Some other methods such as biased coin, minimization and response-
adaptive methods may be applied for specific purposes.

6. 1.SIMPLE RANDOMISATION
Randomization based on a single sequence of random assignments is
known as simple randomization.
This technique maintains complete randomness of the assignment of a
subject to a particular group.
The most common and basic method of simple randomization is flipping
a coin. For example, with two treatment groups (control versus treatment),
the side of the coin (i.e., heads - control, tails - treatment) determines the
assignment of each subject.
Other methods include using a shuffled deck of cards (e.g., even -
control, odd - treatment) or throwing a dice (e.g., below and equal to 3 -
control, over 3 - treatment).
A random number table found in a statistics book or computer-generated
random numbers can also be used for simple randomization of subjects.
This randomization approach is simple and easy to implement in a
clinical research. In large clinical research, simple randomization can be
trusted to generate similar numbers of subjects among groups. However,
randomization results could be problematic in relatively small sample size
clinical research, resulting in an unequal number of participants among
groups.

8. 2.BLOCK RANDOMISATION
Block randomisation is a method used to ensure that the numbers of
participants assigned to each group is equally distributed and is commonly
used in smaller trials.

9. 3.STRATIFIED RANDOMISATION
Stratified randomisation is used to ensure that important baseline
variables (potential confounding factors) are more evenly distributed
between groups than chance alone may assure however, there are limited
number of baseline variables that can be balanced by stratification because
of the potential for small number of subjects within each stratum.

10. 4. UNEQUAL RANDOMIZATION
Most randomized trials allocate equal numbers of patients to
experimental and control groups. This is the most statistically
efficient randomization ratio as it maximizes statistical power for a
given total sample size.
However, this may not be the most economically efficient or
ethically/practically feasible.
When two or more treatments under evaluation have a cost
difference it may be more economically efficient to randomize fewer
patients to the expensive treatment and more to the cheaper one.
The substantial cost savings can be achieved by adopting a smaller
randomization ratio such as a ratio of 2:1, with only a modest loss in
statistical power.
When one arm of the treatment saves lives and the other such as
placebo/medical care only does not much to save them in the
oncology trials. The subject survival time depends on which
treatment they receive.

11. More extreme allocation may be used in these trials to allocate
fewer patients into the placebo group.
Generally, randomization ratio of 3:1 will lose considerable
statistical power, more extreme than 3:1 is not very useful, which
leads to much larger sample size

12. ADVANTAGE
 Eliminates confounding tends to create groups that are comparable for all
factors that influence outcome, known, unknown or difficult to measure .
Therefore, the only difference between the groups should be the intervention
 Eliminates selection bias
 Gives validity in statistical tests based on probability theory.
 This study design can make casual inferences ie, It is the strongest empirical
evidence of a treatment efficacy.
 Randomisation makes groups comparable according both known and
unknown factors.
 Sample size- when adequately powered – avoid both type 1 error ,type 2
error.
 considered as the “Gold standard” – more published

13. DISADVANTAGE
 Does not guarantee comparable groups are difference in confounding
variable may arise by chance.
 Power calculation might demand vast sample size which require more
resources from the investigator.
 A disadvantage of block randomised is that the allocation of participants may
be predictable and results in selection bias when the study groups are
considered.
 Trials which test for efficacy may not be widely applicable trials which test
for effectiveness are larger and more expensive.
 Randomisation requires clinical equipoise: one cannot ethically randomised
patients unless both treatments have equal support in the clinical community.
 Some researcher cannot be ethically performed as an RCT

14. BINDING IN RANDOMISED CONTROLLED TRIALS
Blinding is a process where the critical information on allocation of treatment
is hidden either from the patients, or from observer or the evaluator in the study
The method of blinding RCT is used to ensure that there is no difference in
the way in which each group is assessed or managed and therefore minimized
bias
Bias may be introduced . For example, if the investigator is aware of which
treatment a subject is receiving as this may influence (intentionally or
unintentionally) the way in which outcome data is measured or interpreted.
Similarly a subjects knowledge of treatment assignment may influence their
response to a specific treatment.
Types of blinded study includes- single blinded, double blinded, triple
blinded
A single blind RCT is when the investigator knows but not the study
participants known which treatment has been allocated

15. SINGLE BLINDED RANDOM CONTROLLED TRIAL:
A single blind RCT is when the investigator knows but not the study
participants known which treatment has been allocated (only participant
unaware of the treatment receive)
DOUBLE BLINDED RANDOM CONTROLLED TRIAL:
A double blinding is when neither the investigator (clinician / data
collector)nor the study participants is aware of treatment assignment.
TRIPLE BLINDED RANDOM CONTROLLED TRIAL:
A triple blinded study where participants , investigators (clinician/ data
collectors),evaluator (data analysts/ statistician) are all unaware of the
treatment the participants receives.