This document discusses experimental epidemiology and randomized controlled trials. It defines experimental epidemiology as a model epidemiological method that allows direct control and manipulation of study conditions. Randomized controlled trials (RCTs) involve deliberate intervention or withdrawal in experimental and control groups to observe outcomes. Some key points made include that RCTs provide the strongest evidence of causality but are not always possible or ethical. The document reviews examples of early non-randomized experimental studies in animals and humans and the role of randomization in improving validity. It describes different types of experimental studies and notes alternatives to RCTs such as natural experiments when direct randomization is not feasible.

1. Experimental Epidemiology
Maj Dr Naveen Phuyal
MBBS, MD

2. Randomized Control Trial
Maj Dr Naveen Phuyal
MBBS, MD

3. • The ideal design to use in epidemiological
research settings is an experimental design.
• Experimental epidemiology is a model
epidemiological method.

4. • 1920s: Experimental epidemiology meant
study of epidemics among colonies of
experimental animals such as rats and mice.

5. How does it differ from cohort
studies?
• The conditions in which the studies are carried
out are under direct control of the investigator.
• Involves some action, intervention or
manipulation such as deliberate application or
withdrawal in an experimental group and a
control group
• Observes and compares the outcome of
experiment in both groups

6. Aims of experimental studies
• To provide scientific proof of etiological factors
which may permit modification or control of
disease
• To provide a method of measuring the
effectiveness and efficiency of health services
for the prevention, control and treatment of
disease and improve the health of the
community

7. Experimental studies have all advantages
and disadvantages of cohort studies plus
• Costlier
• Ethical issues
• Feasibility

8. Experimental Studies
ANIMAL STUDIES HUMAN EXPERIMENTS

9. Animal Studies
• Animals have played
important role in men’s
quest for knowledge
about himself.
• Animal studies have
contributed to all
branches of medicine.
Application
• To confirm etiological
hypothesis and study
pathogenic phenomena
• Testing efficacy of
preventive and
therapeutic measures
such as vaccines or drugs
• Completing the natural
history of disease

10. Animal Studies
Advantage
• Can be bred easily
• Multiply rapidly
• Genetic experiments
Disadvantage
• Not all human disease can
be reproduced in animals
• All conclusions drawn may
not strictly apply to humans

11. Human Experiments
• Human experiments will always be needed to
investigate disease etiology and evaluate the
preventive and therapeutic measures

12. • All who drink of this treatment recover in a
short time, Except those whom it does not
help, who all die, It is obvious, therefore, that
it fails only in incurable cases.
Galen[1] (129–c. 199 ce)

13. Sir Francis Galton 1883
• It was asserted by some that men possess the faculty of
obtaining results over which they have little or no direct
personal control, by means of devout and earnest prayer,
while others doubt the truth of this assertion.
• The question regards a matter of fact, that has to be
determined by observation and not by authority; and it is
one that appears to be a very suitable topic for statistical
inquiry. …
• Are prayers answered or are they not? … Do sick persons,
who pray or are prayed for, recover on the average more
rapidly than others?

14. Are prayers answered or are they not?
• 1965: Joyce and Welldon double blind
randomized trial of efficacy of prayer
• 1988: randomized double blind control trial in
CCU

15. Ambroise Pare , 1537 Unplanned trial
• At length my oil lacked and I was constrained to apply in its place a
digestive made of yolks of eggs, oil of roses and turpentine.
• That night I could not sleep at my ease, fearing that by lack of
cauterization I would find the wounded upon which I had not used
the said oil, dead from the poison.
• I raised myself early to visit them, when beyond my hope I found
those to whom I had applied the digestive medicament feeling but
little pain, their wounds neither swollen nor inflamed, and having
slept through the night.
• The others to whom I had applied the boiling oil were feverish with
much pain and swelling about their wounds. Then I determined
never again to burn thus so cruelly the poor wounded.

16. James Lind 1747, Planned trial
• I took 12 patients in the scurvy on board the
Salisbury at sea.
• The cases were as similar as I could have them
… they lay together in one place and had one
diet common to them all.

17. • Two of these were ordered a quart of cider per day. …
Two others took 25 gutts of elixir vitriol. … Two others
took two spoonfuls of vinegar. … Two were put under a
course of sea water. … Two others had two oranges
and one lemon given them each day. … Two others
took the bigness of nutmeg.
• The most sudden and visible good effects were
perceived from the use of oranges and lemons, one of
those who had taken them being at the end of 6 days
fit for duty. … The other … was appointed nurse to the
rest of the sick.

18. Types of experimental studies
1. Clinical (therapeutic) trial- patient suffering from
disease
2. Field trial (preventive trial)- healthy individuals
in the community
3. Community intervention trial- cluster of human
beings
4. Health service evaluation trial
5. Risk factor trial
6. Cessation experiments

19. Randomized Control Trial
Maj Dr Naveen Phuyal
MBBS, MD

21. NON RANDOMIZED TRIALS

22. • Ethical, administrative and other reasons for
which RCT not possible
– Direct experimentation not possible : smoking and
Lung CA
– Some preventive measure can be only be
applicable to small groups in a community (
flouridation)
– When disease frequency is low and natural history
is long ( Cervical Ca)

23. • A crude approach
• Degree of comparability is low
• Chances of spurious results higher
• Validity becomes extra statistical judgment
• Vital decisions in public health have been
made by non-experimental studies

24. Non-randomized trials
• Uncontrolled trials (trials with no comparison groups). Eg.
Pap smear test reduces mortality from Cx CA
• Natural experiments
– cigerrete smoking: smokers vs non smokers
– Natural disasters, atomic bombings, mogrants , social groups,
– “The Great Experiment”
• Before and after comparison studies (eg. James Lind and
scurvy)
– Using a control group
– Without a control group