Experimental Epidemiology: Randomized &

Non-randomized Control Trial..

Dr Jatin Chhaya
Community Medicine Department
SBKS MIRC
 Research studies

2 Dr. Nilesh G. Patel 09/18/2021

INTRODUCTION
Randomized controlled trial (RCT) is so
called because the patients who constitute the
unit of study are allocated into ‘Study group’
(experimental group) and ‘Control group’ at
random, depending upon whether they
receive or do not receive the intervention.

Aim: is to test the efficacy of a new drug or a

new drug regimen or a new therapeutic or
surgical procedure.
Basic steps: In conducting a clinical trial (RCT) are:

a) Drawing of a protocol.
b) Selecting reference population (unit of study).
c) Randomization (allocation into experimental and
control group).
d) Manipulation (intervention).
e) Follow-up.
f) Assessment of outcome.
g) Reporting.
1. Drawing of Protocol
This means specifying the following basic
information before the commencement of the clinical
trial. They are:
Aims and objectives of the study.
Criteria for the selection of study group and
control group.
Size of the sample
Procedures for allocation into study group and
control group.
Intervention to be done (Methodology of
procedure).
The cooperation of the participants till the end of
2. Selection of Reference Population
Reference population is the target population,
to which the results if found successful, are
expected to be applicable.
Reference population, depending upon the
study, could be all suffering from a particular
disease under experiment, e.g. TB/leprosy
patients for new therapy/new regimen or
patients with hernia for new surgical
procedure, etc
3. Randomization (Selection of Study and
Control Group)
This is the ‘Heart’ of the clinical trial. Every
individual has an equal chance of being selected
into either study group or control group, from
the reference population.
Selection of study group (Experimental group):
It is the actual population (or volunteers) derived
from the reference population randomly,
participating in the experiment, still retaining the
same characteristics as the reference population.
Randomization eliminates bias and allows
comparability.
The study group should fulfil the following three
criteria:
It should be ‘Representative’ of the reference
population.
They must give ‘informed consent’, after being
fully informed about the procedure and possible
dangers of the trial.
They must be ‘Susceptible’ to the disease under
study. (i.e. qualified or eligible) Example:
Suppose the trial is on the effect of a new drug
for Anemia, the volunteers must be anemic.
4. Selection of control group.
Another group of the same size as that of the
study group is selected at random from the
reference population, maintaining the similar
characteristics (e.g. age, sex, occupation,
literacy level, income, etc.) as that of the study
group but they do not receive intervention.
5. Manipulation or Intervention
The next step is to intervene or manipulate the
study group by the deliberate application or
withdrawal or reduction of the causal factor,
i.e. new drug, whereas the control group is put
on the inert (or placebo) or the old drug
6. Follow-up
This consists of examination of both the
groups at defined intervals of time
At times, some losses occur to follow-up due
to death or migration or non-cooperation of the
participants.
This is known as ATTRITION. .
7. Assessment of Outcome
This is the final step of clinical trial. The
results may be positive (e.g. the new drug is
better and safer) or may be negative (e.g. the
new drug is not good and/or more hazardous).
The incidence of results (positive or negative)
is compared in both the groups and the
differences are tested for the tests of
significance.
Bias may arise from three sources resulting in errors, as
follows:
1. Subject variation: Patients may report
better/improvement, if they know that they are under
new treatment.
2. Observer bias: Is made by the investigator while
observing.
3. Bias in evaluation: Is made by the investigator
subconsciously.
In order to overcome these errors and bias, a technique
known as ‘Blinding’ is adopted, which is done in three
ways.
4. Single blind trial
5.Double blind trial
Single blind trial: In this type, the participants do not
know whether they belong to study group or control
group. That means they do not know whether they are
receiving new drug or the placebo. However, the
investigator knows who belong to which group. This
trial helps to overcome subject variation.
Double blind trial: In this type, neither the
investigator, (Doctor) nor the participants (patients)
know the group allocation and the treatment (new drug)
received. However, statistician knows it. He assigns the
code numbers and hands over the drugs with code
number to the investigator (doctor) indicating which
one to be given to whom. At the end, the results are
given back to statistician along with the code numbers
for analysis. He will decode and analyse the results.

Triple blind trial: In this type, it goes one step further.

All the participants, doctor and the statistician are
unaware (blind) of the group allocation. The findings of
the trial by the doctor are handed over to the
NONRANDOMIZED TRIALS
Since it is not always possible to resort to randomized
controlled trial in human beings due to ethical, administrative
and other reasons, (e.g. smoking and lung cancer, long period
of follow-up of thousands of people for more than a decade
when the disease frequency is low as in cancer of cervix, etc.)
we can resort to other study designs, such as nonrandomized
(or nonexperimental) trials.
But compared to randomized controlled trials, these are crude,
with more frequent spurious results and of less validity.
So, vital decisions are not made.
These nonrandomized trials are uncontrolled trials, natural
experiments and before and after trials.
Uncontrolled Trials

These are the trials without controls, (comparison

group) because necessity is not felt due to peculiar
nature of the outcome.
For example, in human rabies, the mortality is 100
percent. If a new drug for human rabies is
invented, control group is not required.
In other words, ‘historical controls’ (i.e. experience
of earlier untreated patients) are used.
Natural Experiments

In this type, the ‘natural circumstances’

such as earthquake, famine, floods, etc are
identified as the experiment, because such
events cannot be artificially created for the
sake of the experiments.
Famous example is John Snow’s discovery
that cholera is a water borne disease, was
the outcome of the cholera epidemic in
London in 1852. This was demonstrated
much before the organisms were identified
as the causative agent.
 Before and After Comparison Trials
In this type, the group receiving the intervention
(experiment) itself serves as control.
Classical examples are prevention of scurvy
among sailors by James Lind in 1750, by providing
fresh fruit.
Introduction of seat-belt legislation for prevention
of deaths and injuries caused by motor vehicle
accidents, in Victoria (Australia) (1971).
It was observed that there was definite fall in the
number of deaths and injuries in occupants of car
after the introduction of compulsory seatbelt
legislation.
Thanks & MCQs
1. Neither the investigator, (Doctor) nor the participants
(patients) know the group allocation and the treatment (new
drug) received, is known as:
a) Single Blind Trial
b) Double Blind Trial
c) Triple Blind Trial
d) Uncontrolled Blind Trial
2. Patients may report better/improvement, if they know that
they are under new treatment is known as –
a) Subject variation
b) Observer bias:
c) Bias in evaluation
d) None of above
3. Types of Observational Study is:
a) Randomized Control Trial
b) Uncontrolled trial
c) Cross – sectional Study
d) Natural Experiments
4. Some losses to follow-up occur due to death or
migration or non-cooperation of the participants in
RCT is Known as.
a) Bias in study
b) Attrition
c) Both of above and it is same
d) None of above
5. Cause to effect study is known as?
a) Case control Study
b) Cohort study
c) Non-randomized control trial
d) Randomized Control Trial
Thanks..
Uses of Epidemiology
1. It helps to study the natural history of a disease, i.e.
in relation to agent, host and environmental factors
and further evolution of the disease to its
termination as death or recovery, in the absence of
prevention or treatment.
2. It helps to measure the disease frequency in terms of
the magnitude of the problem (i.e. morbidity and
mortality rates).
3. It helps to make ‘Community diagnosis’ by studying
the distribution of the disease with reference to time,
place and person. Therefore, epidemiology has been
considered as ‘Diagnostic tool’, in community
medicine. Community diagnosis also helps in under-
standing of the social, cultural and environmental
characteristics of the community.
4. Descriptive epidemiology helps to formulate an
‘etiological hypothesis’.
5. It helps to identify the determinants of the disease
and the risk factors.
6. It helps to study historically the rise and fall of the
disease in the population, i.e. As old diseases are
conquered (e.g. smallpox) new diseases have been
identified such as (SARS, AIDS, etc.).
7. It helps to estimate the individual’s risk of a
particular disease by using the indices like Absolute
risk, Atributable risk, Relative risk, Odd’s ratio, etc.
8. It helps to formulate the ‘plan of action’ for
providing the health services including preventive
and control measures.
9. It helps to ‘evaluate’ the health services to find out
whether the measures undertaken are effective in
controlling the disease or not.
10. It helps to make researches in epidemiology.
Thanks..