This document discusses experimental study designs, specifically randomized controlled trials. It begins by defining epidemiology and classification of epidemiological studies. It then describes the aims, process, and key steps of randomized controlled trials: drawing up a protocol, selecting and randomizing populations, implementing interventions, follow-up, and outcome assessment. It also discusses types of RCTs including clinical trials and prevention trials. Blinding techniques are explained. Non-randomized trials are briefly covered.

1. Experimental Study Designs

2. SGD-5,CM7.5
Describe & Discuss
Experimental Study Designs
Date-06/04/2023
Group 1
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3. Epidemiology
• The study of the occurrence and distribution of health-related events, states, and
processes in specified populations, including the study of the determinants
influencing such processes and the application of this knowledge to control
relevant health problems."
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4. Classification of
Epidemiological
studies
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5. Experimental study design
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Aims of experimental studies
(a)To provide ''scientific proof" of aetiological (or risk) factors that may permit the
modification or control of those diseases
(b)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.

6. Experimental study design
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Animal Experiments:
Webster in United States
Topley, Wilson and Greenwood in
England
Classical animal experiments.
Their studies centred round inducing
epidemics in animals and in studies
of herd immunity under laboratory
conditions

7. Experimental study design
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Human Experiments
James Lind Human experiment in which he added different substances to diet
of 12 soldiers who were suffering from scurvy.
Edward Jenner Experiment with Cowpox
Finlay and Reed Experiment to elucidate the mosquito borne nature of yellow
fever.
Goldberger Experiment inducing pellagra by diets deficient in nicotinic acid.

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Experimental studies
Randomized controlled
trials
(RCT)
Non-randomized
or
Non-experimental trials

9. Introduction:
• RCT is an epidemiologic experiment.
• oral hypoglycaemic agents,
• varicose veins stripping,
• tonsillectomy,
• hospitalisation of all patients with myocardial infarction,
• multiphasic screening and applicability of many preventive and therapeutic
procedures.
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Randomized controlled trials (RCT)

10. Basic steps in conducting RCT:
1. Drawing up a protocol
2. Selecting reference and experimental population
3. Randomization
4. Manipulation or intervention
5. Follow-up
6. Assessment of outcome.
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Randomized controlled trials (RCT)

11. Design of Randomized Control Trial:
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Select suitable population
(Reference or Target population)
Select suitable sample
(Experimental or study population)
Make necessary exclusions
Those not eligible
Those who do not wish to
give consent
RANDOMIZE
Experimental
group
Control group
Manipulation and follow-up ASSESSMENT
Randomized controlled trials (RCT)

12. 1. Drawing up a protocol:
• 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-
When and where, and how to what kind of patients,
Standardization of working procedures and
Schedules as well as responsibilities of the parties involved in the trial, up to the stage
of evaluation of the outcome of the centres participating in the trial.
• The protocol aims to prevent bias and reduce the study's sources of error.
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Randomized controlled trials (RCT)

13. 2. Selecting reference and experimental
populations:
a) Reference or Target population: It is the population to which the findings of the trial if
found successful, are expected to be applicable (e.g., a drug, vaccine or other procedures).
b) Experimental or study population: It is derived from the reference population. It is the
actual population that participates in the experimental study.
• The participants or volunteers must fulfil the following criteria:
- They must give informed consent.
- They should be representative of the population to which they belong.
- They should be qualified or eligible for the trial.
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Randomized controlled trials (RCT)

14. 3. Randomization:
• Randomization is a statistical procedure by which the participants are allocated
into groups, usually called “study” and “control” groups, to receive or not to
receive experimental preventive or therapeutic procedures, manoeuvres or
interventions.
• Randomization is an attempt to eliminate bias and allow for comparability.
• Randomization is the heart of a clinical trial.
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Randomized controlled trials (RCT)

15. 4. Manipulation:
• Intervene or manipulate the study (experimental) group by applying, withdrawing,
or reducing the suspected causal factors.
• Manipulation creates an independent variable (e.g., drug, vaccine, a new
procedure) whose effect is then determined by measurement of the final outcome,
which constitutes the dependent variable (e.g., the incidence of disease, survival
time).
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Randomized controlled trials (RCT)

16. 5. Follow-up:
• This implies the examination of experimental and 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 the final assessment of the
outcome.
• The follow-up may be short or require many years, depending on the study
undertaken.
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Randomized controlled trials (RCT)

17. 6. Assessment:
The final step is an assessment of the outcome of the trial in terms of :
a) Positive results: Benefits of the experimental measures such as reduced incidence or
severity of the disease, the cost to the health service or other appropriate outcomes in
the study and control groups.
b) Negative results: severity and frequency of side effects and complications.
• Bias may arise from errors of assessment of the outcome due to human element. May be
from the three sources:
- Bias on the part of the participant
- Observer bias
- Bias in evaluation
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Randomized controlled trials (RCT)

18. Blinding:
Blinding can be done in three ways:
a) Single Blind Trial: The participant is unaware whether he belongs to the study
or the control group.
b) Double Blind Trial: Neither the doctor nor the participant knows the group
allocation.
c) Triple Blind Trial: The participant, the investigator, and the person analysing
the data are all blind.
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Randomized controlled trials (RCT)

19. Types of RCT:
1. Clinical trials
2. Preventive trials
3. Risk factor trials
4. Cessation experiments
5. Trial of etiological agents
6. Evaluation of health services
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Randomized controlled trials (RCT)

20. 1. Clinical trials:
• For the most part, clinical trials have been concerned with evaluating therapeutic agents,
mainly drugs.
- Evaluation of beta blockers in reducing cardiovascular mortality in patients surviving the
acute phase of myocardial infarction.
- Trials of folate treatment/ supplementation before conception
- Trials of aspirin on cardiovascular mortality
- Efficacy of tonsillectomy for recurrent throat infection.
• Unfortunately, not all clinical trials are susceptible to being blinded.
• Many ethical, administrative and technical problems are involved in the conduct of clinical
trials.
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Randomized controlled trials (RCT)

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23. 2. Preventive trials (Field trial):
• Preventive 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.
• Analysis of a preventive trial must result in a clear statement.
A) The benefit the community will derive from the measure
B) The risks involved
C) The costs to the health service in terms of money, men and material resources.
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Randomized controlled trials (RCT)

24. 3. Risk factor trials:
• A type of preventive trial is the trial of risk factors in which the investigator intervenes to
interrupt the usual sequence in the development of disease for individuals with “risk
factors” for developing the disease.
• Risk factor trials can be a single factor or multi-factor.
• Example:
• The major risk factors for coronary heart disease are elevated blood cholesterol,
smoking, hypertension, and sedentary habits.
• Main possibilities of intervention in coronary heart disease are the reduction of blood
cholesterol, the cessation of smoking, the control of hypertension, and the promotion
of the regular physical activity.
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Randomized controlled trials (RCT)

25. 4. Cessation experiments:
• Another type of preventive trial.
• An attempt is made to evaluate the termination of a habit which is considered to be
causally related to a disease.
• The example is cigarette smoking and lung cancer.
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Randomized controlled trials (RCT)

26. 5. Trial of aetiological agents:
• One of the aims of experimental epidemiology is to confirm or refute an
aetiological hypothesis.
• The best-known example trial of an aetiological agent relates to retrolental
fibroplasia.
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Randomized controlled trials (RCT)

27. 6. Evaluation of health services:
• Randomized control trials have been extended to assess the effectiveness and
efficiency of health services.
• The necessity of choice arises from the fact that resources are limited, and
priorities must be set for the implementation of a large number of activities that
could contribute to the welfare of society.
• An excellent example of such an evaluation is the controlled trials in the
chemotherapy of Tuberculosis in India.
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Randomized controlled trials (RCT)

28. Introduction:
• Approach is sophisticated in randomised control trials but rather crude in non-
randomized trials.
• As there is no randomisation in non-experimental trials, the degree of
comparability will be low and the chances of a spurious result higher than where
randomisation had taken place.
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Non-randomized / Non-experimental trials

29. Examples-
1. Uncontrolled Trial:
There is room for uncontrolled trials (i.e., trials with no comparison group)
• Example-
• There were no randomised controlled studies of the benefits of the pap test when it was introduced.
• Today, there is indirect epidemiological evidence from well over a dozen uncontrolled cervical
cancer screening studies that the pap test effectively reduces mortality from the disease.
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Non-randomized / Non-experimental trials

30. 2. Natural Experiments:
• Where experimental studies are not possible in human populations, the
epidemiologist seeks to identify “natural circumstances” that mimic an
experiment.
• Example- In respect of cigarette smoking, people have separated themselves
“naturally” into two groups, smokers and non-smokers. Epidemiologist tested
hypotheses regarding lung cancer and cigarette smoking.
• John Snow’s discovery that cholera is a water-borne disease was the outcome of a
natural experiment.
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Non-randomized / Non-experimental trials

31. 3. Before and After comparison studies:
These are community trials that fall into distinct groups:
a) Before and after comparison studies without control.
b) Before and after comparison studies with control.
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Non-randomized / Non-experimental trials

32. Exercise-
• The TB chemotherapy centre wants to determine the relative risk for contact with
patients treated at home and sanatorium.
• A controlled comparison of home and sanatorium treatment of TB for one year
and subsequently for another four years to study the emergence of relapse cases in
these two groups.
• If you are the immunisation officer of your district and want to check the efficacy
of the measles vaccine, how will you proceed?
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Randomized controlled trial
Randomized controlled trial
Field trial

33. Thank you…..
Keep Doing Experiments….