EXPERIMENTAL

EPIDEMIOLOGY

R.Jinisha Virgin
IV.B.D.S
EPIDEMIOLOGY:

The epidemiology is the study of distribution

and determinants of disease frequency in man.

-
MacMahon(1960)
Descriptive
epidemiology

Analytical epidemiology
METHODS
Experimental
epidemiology
Experimental epidemiology:

 Studies carried out under the direct control of the investigator.

 Involve some action, intervention or manipulation such as
deliberate application or withdrawal of the suspected cause or
changing one variable in the causative chain in the experimental
group , while making no change in the control group, and observing
and comparing the outcome of the experiment in both the groups.
 To provide
scientific
proof

AIM
To provide
a
measuring
method
 Advantages:
Experimental studies may be • Animals can be bred in laboratories and
conducted in animals or humans.
manipulated easily by the investigators

Animal studies are done to • They multiply rapidly and are useful for
Experimentally reproduce human certain experiments which, in humans would
disease to confirm etiological hypothesis. have taken several years to complete.

Study the pathogenic phenomena and

complete the natural history of disease.
Limitations:
• All human disease cannot be reproduce in
Test the efficacy of preventive or animals
therapeutic measures.
• All conclusions derived from animal studies
may not be strictly applicable to humans
 •Randomized controlled trials

Types
•Non-randomized or non-experimental trials
 Randomized controlled trials

Selecting reference
Drawing up a and experimental Randomization
protocol populations

Manipulation or Assessment of
Follow-up
intervention outcome
Randomized
controlled trials:
• Drawing up a protocol
• Selecting reference and
experimental populations
• Randomization
• Manipulation or intervention
• Follow-up
• Assessment of outcome
• The protocol specifies the aims and
objectives of the study, questions to
be answered, criteria for the
selection of study and control groups,
size of the sample, the procedures
for allocation of subjects into study
and control groups, treatments to be
applied.
 Randomized
controlled trials:
• Drawing up a protocol
• Selecting reference and
experimental populations
• Randomization
• Manipulation or intervention
• Follow-up
• Assessment of outcome
(a)Reference or target population :
It is the population to which the
findings of the trial are expected to be
applicable
A reference population may
be as broad as mankind or it may be
geographically limited or limited to
persons in specific age, sex,
occupational or social groups.
(b) Experimental or study population :
The study population is
derived from the reference population. It
is the actual population that participates
in the experimental study.
Randomized
controlled trials:
• Drawing up a protocol
• Selecting reference and
experimental populations
• Randomization
• Manipulation or intervention
• Follow-up
• Assessment of outcome
• Statistical procedure by which the
participants are allocated into groups usually
called "study" and "control" groups, to
receive or not to receive an experimental
preventive or therapeutic procedure.
• An attempt to eliminate "bias" and allow for
comparability.
Randomized
controlled trials:

• Drawing up a protocol

• Selecting reference and experimental

populations • Having formed the study and control groups,
• Randomization the next step is to intervene or manipulate
• Manipulation or intervention the study (experimental) group by
deliberate application or withdrawal or
• Follow-up
reduction of the suspected causal factor
• Assessment of outcome
Randomized
controlled trials:

• Drawing up a protocol

• Selecting reference and experimental • Examination of the experimental and control

populations group subjects at defined intervals of time,
• Randomization in a standard manner, with equal intensity,
•
under the same given circumstances, in the
Manipulation or intervention
same time frame till final assessment of
• Follow-up
outcome.
• Assessment of outcome
• Some losses to follow-up are inevitable due
to factors, such as death, migration and loss
of interest. This is known as attrition.
 • The final step is assessment of the outcome
Randomized
of the trial in terms of
controlled trials:
• Positive results : benefits of the
experimental measure such as reduced
incidence or severity of the disease .
• Drawing up a protocol
• Negative results: severity and frequency of
• Selecting reference and experimental
side-effects and complications, including
populations
death
• Randomization
• Bias may arise from errors of assessment of
• Manipulation or intervention
the outcome due to human element.
• Follow-up
• To reduce bias , Blinding can be done:
• Assessment of outcome
Single Double Triple
blind trial blind trial blind trial

BLINDING
 Some study designs
Concurrent parallel study
designs :
• comparisons are made between two
randomly assigned groups, one group
exposed to specific treatment, and
the other group not exposed.
Cross-over type of study designs
• each patient serves as his own control
• the patients are randomly assigned to a study
group and control group.
• The study group receives the treatment under
consideration.
• The control group receives some alternate form
of active treatment or placebo.
• The two groups are observed over time.
• Then the patients in each group are taken off
their medication or placebo to allow for the
elimination of the medication from the body and
for the possibility of any "carry over" effects
• After this period of medication the two groups
are switched. Those who received the treatment
under study are changed to the control group
therapy or placebo, and vice versa.
 Clinical trials

Preventive trials

Risk factor trials

Randomize
d controlled Cessation experiments
trials
Trial of etiological agents

Evaluation of health services

Community intervention trials

Randomized
controlled trials:

• Clinical trials
• Preventive trials • "Clinical trials" have been concerned with
• Risk factor trials evaluating therapeutic agents, mainly drugs.
• Cessation experiments eg. Trials of folate
• Trial of etiological agents treatment/supplementation before conception to
prevent recurrence of neural tube defects
• Evaluation of health
services
• Community intervention
trials
 PHASES OF CLINICAL TRIALS

PHASES DOSING NO.OF SUBJECTS MAIN GOAL

0 Subtherapeutic About 10 Pharmacokinetics and

Pharmacodynamics
I Ascending dose 20-100 Dose-ranging

II Therapeutic dose 100-300 Drug efficacy

III Therapeutic dose 300-3000 Therapeutic effect

IV Therapeutic dose Anyone seeking treatment Long-term effects

V No dosing All reported use Research on data collected

Randomized
controlled trials:
• Clinical trials
• Preventive trials
• Risk factor trials
• Cessation experiments
• Trial of etiological agents
• Evaluation of health
services
• Community intervention
trials
• The term "preventive trials" implies trials of
primary preventive measures.
• These trials are purported to prevent or
eliminate disease on an experimental basis.
• The most frequently occurring type of
preventive trials are the trials of vaccines and
chemoprophylactic drugs.
• For example, in 1946, the Medical Research
Council of UK conducted an extensive trial to
test whooping cough vaccine from three
manufacturers in ten separate field trials.
Randomized
controlled trials:
• Clinical trials
• Preventive trials
• Risk factor trials
• Cessation experiments
• Trial of etiological agents
• Evaluation of health
services
• Community intervention
trials
• A type of preventive trial
• The trial of risk factors in which the
investigator intervenes to interrupt the usual
sequence in the development of disease for
those individuals who have "risk factor" for
developing the disease.
• For example, the major risk factors of
coronary heart disease are elevated blood
cholesterol, smoking, hypertension and
sedentary habits.
 Randomized
controlled trials:
• Clinical trials
• Preventive trials
• Risk factor trials
• Cessation experiments
• Trial of etiological agents
• Evaluation of health services
• Community intervention trials
• In this type of study, an attempt is made to
evaluate the termination of a habit (or
removal of suspected agent) which is
considered to be causally related to a
disease.
• The familiar example is cigarette smoking
and lung cancer.
• If in a randomized controlled trial, one group
of cigarette smokers continue to smoke and
the other group has given up, the
demonstration of a decrease in the incidence
of lung cancer in the study group greatly
strengthens the hypothesis of a causal
relationship.
Randomized
controlled trials:

• Clinical trials
• Preventive trials
• Risk factor trials
• Cessation experiments
• Trial of etiological agents
• Evaluation of health services
• Community intervention trials
• One of the aims of experimental
epidemiology is to confirm an aetiological
hypothesis.
• Since most diseases are fatal, disabling or
unpleasant, human experiments to confirm
an aetiological hypothesis are rarely possible
.
Randomized
controlled trials:

• Clinical trials
• Preventive trials • Randomized controlled trials have been
• Risk factor trials extended to assess the effectiveness and
efficiency of health services..
• Cessation experiments
• Trial of etiological agents
• Evaluation of health services
• Community intervention trials
Randomized
controlled trials:
• Clinical trials
• Preventive trials
• Risk factor trials
• Cessation experiments
• Trial of etiological agents
• Evaluation of health services
• Community intervention
trials
• Usually carried out in hospitals or clinics and
are usually directed at a patient group with
specific health condition.
• E.g. Testing of vaccine
• Randomization is done on communities
rather than individual
• Contamination occurs when individual from
one of the experimental groups receives the
intervention from other experimental groups
• Co intervention occurs when other
interventions , either unknown to the
investigators or otherwise ,are
simultaneously introduced, in which case
,comparison of results from 2 randomized
group will no longer be a reflection of
intervention under trial
 NON-RANDOMIZED TRIALS

• Although the experimental method is almost always to be preferred, it is not

always possible for ethical, administrative and other reasons to resort to a
randomized controlled trial in human beings.
• For example, smoking and lung cancer and induction of cancer by viruses
have not lent themselves to direct experimentation in human beings.
• There is no randomization in non-experimental trials, the degree of
comparability will be low and the chances of a spurious result higher than
where randomization had taken place.
 EXAMPLES

Before and
Natural Uncontrolle after
experiments d trials comparison
studies
 • Trials with no comparison group.
• Uncontrolled trials • Initially uncontrolled trials may be useful in
evaluating whether a specific therapy
• Natural experiments
appears to have any value in a particular
disease, to determine an appropriate dose,
• Before and after to investigate adverse reactions, etc.
comparison studies
 • Where experimental studies are not possible
• Uncontrolled trials
in human populations, the epidemiologist
• Natural seeks to identify "natural circumstances"
experiments that mimic an experiment.
• Eg..John Snow's discovery that cholera is a
• Before and after water-borne disease was the outcome of a
comparison studies natural experiment.
 • Before and after comparison studies without
control
comparing the incidence of disease
before and after introduction of a preventive
measure.
• Natural experiments
eg. the prevention of scurvy among
• Uncontrolled trials sailors by James Lind in 1750 by providing fresh
• Before and after fruit.
comparison studies • 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 .
 CONCLUSION

• The most outstanding contribution of epidemiology is the study of association

and causation in health and disease.
• Ironically , this is also the most difficult field in epidemiology ,since it is often
not easy to tell whether an observed association between a condition and a risk
factor represents a cause and effect relationship.
 • ESSENTIALS OF PUBLIC HEALTH
Reference: DENTISTRY
-SOBEN PETER(6TH
edition)