summarize the content for 10 marks - EXPERIMENTAL STUDIES
12.7.1. Introduction
Designs of survey are fully observational. The Investigators study people as they find
them. Therefore, subjects exposed to a risk factor often vary from that of unexposed in
other means that affect risk of disease. When the confounding affects are recognized in
advance, then it can be helpful in the design and analysis of the study. Still there is a
chance of unrecognised confounders.
Observational studies are fewer susceptible to confounding as it is easy to determine who
is exposed and who is unexposed. When the exposure is done randomly and persons or
number of groups randomised is in large number then the unrecognised confounding
effects become statistically unlikely. There are some ethical restrictions on observational
study in persons, and it is not satisfactory to expose subjects deliberately to theoretically
serious risks. This bound the application of observational methods in the detection of
disease aetiology, although it is easy to evaluate preventive strategies experimentally.
For example, the companies involving in a coronary heart disease prevention project
were assigned to 2 groups. The one group is receiving health education program and a
programme of screening for coronary risk. The other group are left alone. The disease
incidence was then compared among the 2 groups. The application of observation
studies, though, is in estimating therapeutic interferences by randomised organised trials.
12.7.2. Randomised Controlled Trials
In randomised controlled trial, the criteria for entrance to the study sample must be
specified (e.g., in terms of age, sex, diagnosis, etc.). As in other epidemiological
investigations, the subjects studies must be descriptive of target population in whom it is
expected to apply the effects.
260 Biostatistics & Research Methodology
In a series of hospital patients, comparison of 2 treatments for rheumatoid arthritis may
not provide a reliable guide to managing the less severe range of the disease. The subjects
fulfilling the criteria of entrance are inquired to consent to participation. When the refusal
rates are high a decision should be made as to how far the helpers that remain can be
considered descriptive of the target population.
The particular subjects to join are then randomised to treatments under assessment. By
using published tables of random numbers or by random numbers produced with
computer, this can be achieved. Once the subjects arrives the study serially (e.g., as
patients are admitted to hospital) then the randomisation is done in blocks. Therefore in
study of comparing between two treatments say, A and B, the patients might be
randomised in six blocks. When the first 6 patients entering the trial then 3 would be
assigned to treatment A and 3 to treatment B in random manner. To allocate treatments in
each successive set of 6 patients, the similar techniques would be used.
It prevents large imbalances in the numbers of patients assigned to different treatments.
This is the main advantage of such techniques. This could occasionally happen
sometimes by accidentally. It also confirms that the balance among the dissimilar
treatments is unevenly constant during the study, therefore decreasing the chance for
confounding by extraneous variables that change.
Occasionally major determining factor of result can be recognised at the time when
subjects arrived for the study. For example, during a trial of treatment for serious
myocardial infarction, the presence of certain dysrhythmias on admission to hospital
might be a significant index of prognosis. Such prognostic markers will tend to be evenly
distributed among the dissimilar treatments groups and it is the part of randomisation.
Through, as more insurance against inadvertent confusing, there is the chance to stratify
subjects at entry as per prognostic variable (for example, selecting patients with and
without dysrhythmias) and then randomise them within blocks.
Once result is prompted through other factors of a patient’
s management, as well as
through the treatments under assessment, it may be needed for those responsible for
organisation to be “blinded” to which treatment has been assigned
From the objective result, the end point of trials varies, for example, haemoglobin
concentration or birth weight, to extra physical signs and subjective symptoms.
For example, when a fresh analgesic for migraine is being calculated on the basis of
symptoms, a pharmacologically inactive placebo can be used for comparison. Or else,
there is a hazard that patients will observe an advantage simply since they are receiving
something fresh.
It is significant always to compare subjects according to the treatment to which they were
randomised, even in case, this treatment was not completed.
For example, when a blocker is compared with placebo to reduce mortality in a trial after
myocardial infarction, patients were withdrawn from treatment in case they developed
severe heart failure -complication of B blockers.
12.7.3. Crossover studies
Crossover design is the result of the modification of randomised controlled trial. This is
mainly valuable when result is measured by reports of subjective symptoms. It can only
be useful when the treatments are short lived (e.g., pain relief from the analgesic).
Designing the Methodology (Chapter 12) 261
The eligible patients who have agreed to join receive each treatment sequentially in a
crossover study, often with a “washout” period among treatments to eliminate any carry
over effects. Though the treatments are randomised, so patients obtain them in different
order. Result is checked during every period of treatment, and thus each patient can serve
as his control.
12.7.4. Experimental Study of Populations
The experimental studies allocate and compare treatments among separate subjects, and
then it is also imaginable to carry out experimental interventions at level of populations.
A coronary heart disease prevention project in which the units of study were the
workforces of dissimilar factories.
Interventions in population can be randomly allocated as in the studies of individuals.
Therefore, when the number of populations under assessment is small then randomisation
might not be useful. In its place, it might be improved to allocate interventions in a preplanned way to confirm maximum comparability among different intervention groups.
Control of residual confounding can be supported by comparing the study and control
populations before and after the intervention is presented