EXPERIMENTAL

EPIDEMIOLOGY

DR m a thaher
Pg 1st year
COMMUNITY MEDICINE 07/04/2015

HYPOTHESIS

THE SMOKING OF 30-40

CIGARETTS PER DAY CAUSES
LUNG CANCER IN 10%
OFSMOKERS AFTER 20
YEARS OF EXPOSURE

EPIDEMIOLOGY
METHODS
1.OBSERVATIONAL STUDIES
A.DESCRIPTIVE
STUDIES

2.EXPERIMENTAL
STUDIES

B.ANALYTICAL
STUDIES

1.ECOLOGICAL
2.CROSS-

INTERVENTIONAL STU
A.RCT

SECTIONAL
3CASE-

B.FIELD TRIALS

CONTROL
4.COHORT

C.COMMUNITY TRIALS

EXPERIMENTAL
EPIDEMIOLOGY

In the 1920s,experimental epidemiology

meant the study of epidemics among colonies
of experimental animals such as rats and
mice.in
modern
usage,experimental
epidemiology is often equated with RCT.
AIMS
To provide a scientific proof.
To provide a measuring method.

Animal studies

At the beginning of this century

,,WEBSTER(us)andTOPLEY,WILSONand
GREENWOOD(england) carried out animal
experiments.
ADVANTAGES
Experimental
animals
can
be
bred
inlab,manpulated
easily
according
to
investigator wishes.
Multyply rapidly

Animal studies

Limitations:

Not all the diseases reproduse in animals.

All the conclusions derived from animal
experiments may not be strictly appicable
to human beings.
EX:-WHO trial on
typoid vaccine.-Almorth
Wright
RCT
trials.

HUMAN EXPERIMENTS

Human experiments will always be needed to

investigate disease aetiology and to evaluate
the preventive and therapeutic measures.
These studies are even more essential in the
investigation of diseases that cannot be
reproduced in animals.
Ex: JAMES LIND
EDWARD JENNER
GOLDBERGERS EXPERIMENT.

 Although the experimental method is

unquestionably the most incisive approach to
scientific problem, ethical and Iogistic considerations
often prevent its application to the study of disease
in humans.
Therefore, before launching human experiments,
the benefits of the experiment have to be weighed
against risks involved.
The volunteers should be made fully aware of all
possible consequences of the EXPERIMENT.
Thus when an illness is fatal (e.g., excessive
haemorrhage) and the benefit of treatment (e.g.,
blood transfusion) is self-evident, it would be
ethically unacceptable to prove or disprove the
therapeutic value of blood.

 However, such instances represent only a

small part of the total research effort.
On the other hand, in the present era of
scientific medicine, many unscientific or
scientifically unsound procedures are still
being carried out.
EX;diethylstilbesteral-ca.vagina.
The WHO in 1980 has laid down a strict code
of practice in connection with human trials.

Experimental studies are two

types.
A. RCT

RANDOMIZED
CONTROL
TRIALS

It IS really an epidemiologic experiment.

Since its introduction. The RCT has

questioned the validity of such widely used
treatments as oral hypoglycemic agents,
varicose vein stripping, tonsillectomy, etc

For new programmes or new therapies, the

RCT is the No.1 method of evaluation.

Basic steps in RCT conducting:

1.Drawing up a protocol.
2.Selecting reference and experimental
populations.
3.Randomization .
4.Manipulation or intervention
5.Follow up
6.Assessment of outcome

1.The protocol
It specifies:Aims &objectives of study
Questions to be answered
Criteria for selection of study and control
groups
Size of sample
The procedures for allocation of subjects into
study and control groups.
Treatment to be applied.
Standardization of working procedures
Schedules and responsibilities of the parties

Protocol
AIM:

preventing bias and to reduce the

source of errors in the study.

Preliminary test runs: some times it is

useful to have short test to run of the
protocol to see any flaws

SELECTING REFERENCE
&EXPERIMENTAL
POPULATION

REFERANCE POPULATION: Population to which the findings of the trail are

expected to be applicable.
Ex :-specific age group people
geographically limited
population of school children

EXPERIMENTAL POPULATION

it is derived from reference population.

It is the population that actully
participates in experimental studies.
Participants must fullfil 3 criterias.
1.must give informed consent
2.should be representative of the
population.
3.should be eligible for the trail.

RANDOMIZATION

it is a statistical procedure by which

participents allocated in to study and
control groups.
it is a heart of RCT

It is an attempt to eliminate bias and allow for

comparability.
It will give greatest confidence that the groups
are comparable so thatlike can be compared
with like.

Randomization

Randomization
is done only after the
participants entered the study,that is after
having been qualified for the trial and has
given informed consent to participate in study.
Randomization best done by using a table of
random
numbers.(simple
random
sample).random numbers are a haphazard
collection of certain numbers,arranged in a
cunning manner to eliminate personal
selection of unconscious bias in taking out the
sample.

MANIPULATION

After selection of study& control

group,intervene the study group by deliberate
application(vaccine, drug) as laid down in
protocol.
This manipulation creates an independent
varieble (e.g. drug,vaccine)whose effect is
then determined by measurement of the final
outcome,which constitutes the dependent
varieble(incidence of disease,survival time.)

FOLLOW-UP

This implies examination of the experimental

& control group subjects at defined intervals of
time,in a standard manner,with equal
intensity,under
the
same
given
circumstances,in the same time frame till final
assessment of outcome.
Attrition:-some cases losses to follow-up due
to death,migration,loss of intrest.
If the attrition is substantial,it may be difficult
to generalise the results to refferens
population.

ASSESSMENT

POSITIVE RESULTS:-Benefits of experiment

measurers reduced incidence or severity of
disease..
NEGATIVE RESULTS:-Severity and frequency of
side-effects and complications,if any,including
death.

BIAS

Bias may arise from errors of assessment of the

outcome due to human element.these may be
from 3 sourses.
First
- bias from the
participants,who may
subjectively feel better or report improvement if
they knew they were receiving a new form of
treatment.known as subjective variation.
Second investigater measuring the outcome of a
trial may be influnced if he knows beforehand the
particular therapy to which the pt has subjected.
(observer variation)

Third there may be bias in evaluation.-the

investigator may give subconsciously give a
favorable report of the outcome of trial.

BLINDING:-In

order to reduce above

problems,blinding is adapted .it can be done
in 3 ways.

A.Single blind trials:-participant is not aware

of group allocation.

B.Double blind trials:-neither doctor nor

participant is aware of group allocation.& Rx
received.

C.Triple blind trials:-participant,investigater

and person analysing data are blind.

STUDY DESIGNS

1.Concurrent parallel study

designs
2.Cross over type of study design.

Concurrent parallal
study designs.

Cross over type of study

design

Types of RCT-1.clinical

trials

For the most part,clinical trials

have been
concerned
with
evaluting
therapeutic
agents,mainly drugs.
Eg: trials of folate- to prevent NTD.
efficacy of tronsillectomy for
recurrent
throat infections.
Many ethical, administrative, & technical
problems are involved in the conduct of clinical
trials.

2.Preventive trials

It implies primary prevention.

Most common trials are done vaccines &
chemoprophilactic
Eg: Medical research concil of UK woophing cough
since preventive trials involve larger number of
subjects and longer time span to obtain
results,there may be greater number of practical
problems in their organisation and execution.

3.Risk factor trial

A type of prevenive trials in which he investigator

internvenes to interrupt the usual sequence in
the development of disease for those individual
who has risk factor in developing the disease
Often this involves risk factor modification
Eg. CHD- 4 major risk factor- WHO studyclofibrate therapy
OSLO study, MRFIT in US

Cessetion
experiments

Another type of preventive trial is ihe cessation

experiment. In this type of study, an attempt is
made to
evaluate the termination of a habit (or removal of
suspectedagent) which is considered to be
causally related to a disease.
If such action is followed by a significant
reduction in the disease, the hypothesis of cause
is greatly strengthened.
Ex :cigarette smoking-lung cancer.

5.Trial of etiological agents

One of the aim of experimental etiology is to

confirm or refute etiological hypothesis.
eg;: RLF
Since most disease are fatal,disabling,
human experiments to conform an aetiological
hypothesis are rarely possible.

6.Evaluaton of health
services

RCT have been extended to assess the

efectiveness & efficiency of health services.
Eg: Domicilliary treatment- pulm. Tuberculosis.

Health services research studies.

Non Randamized
Trials

Due to ethical, administrative, cost it is not

always possible to resort to RCT.

Approach is crude. As there is no

randamisation, degree of comparability will be
low and chances of spurious results will be
high.

Examples of non randamized trials

1. Uncontrolled trials:
Trials with no comparision groups.
Useful to known whether specific therapy
is valuable for particular disease, to
determine the appropriate dose, to
investigate adverse reaction.
Eg:indirect epidemiological evidence that
the pap test is effective in reducing
mortality from cervical cancer.

Non-randomized
trials

2. Natural experiments:

Where experimental studies are not possible in

human beings, some natural circumstances
mimics as experiment
Eg: smokers and non smokers- lung cancer.
John snow discovery- cholerawater born disease.

John snows experiment

Non-Randomized
trials

3.BEFORE AND AFTER COMPARISON STUDIES:

These community trials fall into 2 distinct groups.

A.Before & after comparison studies without control.

B.Before & after comparison studies wth control

Before &after comparison

studies without control

These studies centre round comparing the

incidence ofdisease before and after
introduction of a preventive measure.
The events which took place prior to the use
of the new treatment or preventive procedure
are used as a standard for comparison.
In other words, the experiment serves as its
own control; this eliminates virtually all group
differences.

Ex:James Lind scury experiment

Prevention of polio by salk and sabin
vaccine
In order to establish evidence in before and after
comparison studies, the following are needed; (a) data
regarding the incidence of disease, before and after
introduction of a preventive measure must be available
(b) there should be introduction or manipulation of only
one factor or change relevant to the situation, other
factors remaining the same.
as for example, addition of fluorine to drinking water to
prevent dental caries
(c) diagnostic criteria of the disease should remain the
same
(d) adoption of preventive measures should be over a
wide area
(e) reduction in the incidence must be large following
the introduction of the preventive measure, because
there is no control.

Effect ofadoption of compulsory seat-belt

legislation in vectoria,Aus-1971

1970

1971

%change

deaths

564

464

-17.7

injuries

14620

12454

-14.8

Before and after comparison studies

with control

In the absence of a control group, comparison

between observations before and after the use

of a new treatment or procedure may be
misleading.
In such situations, the epidemiologist tries to
utilize a "natural" control group i.e., the one
provided by nature or natural circumstances.
If the preventive programme is to be applied to
an entire community. he would select another
community as similar as possible, particularly
with respect to frequency and characteristics of
the disease to be prevented.

Effect of adaptation of compulsary

seat-belt legislation in victoria
comparing with other states(where
legislation not applied)
1970

1971

%change

DEATHS
Victoria
Other states

564

464

1426

1429

-17.7
0.2

INJURIES
Victoria
Other
states

14620

12,454

-14.8

39,980

40,396

1.0

Advantages

Scientifically ideal method.

Removes a large number of biases related to
selection and measurement,
Ensures temporal relationship between
exposure and outcome.
Builds up faith in the findings of the study.

Disadvantages

In many situations, rspecially those which

concern study of risk factors or prognostic
factors,one can not randomly allocate human
beings into two groups.
Eg ;-smoking- lung cancer
Ethical issues.
Expensive
Long time need..

THANK YOU