a ppt on different types of experimental epidemiological study designs

1. Experimental Studies
-- Dr. Dipayan Banerjee
DHA final year
NIHFW

2. Introduction
• In 1920s the experimental epidemiology meant the study of
epidemics among colonies of experimental animals such as rats and
mice. In modern usage it is equated with Randomized control trial
• Experimental studies are considered to be the best kind of study
design as it is most scientifically rigorous method of hypothesis
testing evaluating the effectiveness or intervention
• 2 types: Animal study
• Human study

3. Aim
• 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 prevention, control and treatment of disease and
improve the health of community

4. Animal study
• Applications:
• To confirm etiological hypothesis and study pathogenic phenomenon
• Testing efficacy of preventive and therapeutic measures of vaccines/drugs
• Completing the natural history of disease
• Advantage:
• Can be bred easily
• Multiply rapidly
• Genetic experiments
• Lesser ethical issues
• Disadvantage:
• Not all human disease manifests same in animals
• All conclusions drawn may not strictly apply to human

5. Steps of Experimental study
• Drawing up a protocol
• Identifying reference population
• Sample population
• Exclusions
• Randomization of experimental and control group
• Manipulation/Intervention
• Follow up
• Assessment of outcome

6. Human trials
• Classification:
• Randomized control trials
• Non Randomized control trials

7. Randomized Control Trials

8. • The most commonly encountered experiment in health science
research, and the research strategy by which evidence of effectiveness
is measured, is the randomized, controlled, double-blind clinical trial,
commonly known as an RCT.
• Types:
• Clinical trials
• Preventive trials
• Risk factor trials
• Cessation experiments
• Trial of etiological agents
• Evaluation of health services

9. Classification
• By study design:
• Parallel-group – each participant is randomly assigned to a group, and all the
participants in the group receive (or do not receive) an intervention.
• Crossover – over time, each participant receives (or does not receive) an intervention
in a random sequence.
• Cluster – pre-existing groups of participants (e.g., villages, schools) are randomly
selected to receive (or not receive) an intervention.
• Factorial – each participant is randomly assigned to a group that receives a particular
combination of interventions or non-interventions

10. • By outcome of interest:
• Explanatory – Test efficacy in a research setting with highly selected participants and
highly controlled conditions
• Pragmatic – Test effectiveness in everyday practice with relatively unselected
participants and under flexible condition
• By hypothesis:
• Superiority trials – intervention is hypothesized to be superior to another in a
statistically significant way
• Noninferiority trials – to determine whether a new treatment is no worse than a
reference treatment
• Equivalence trials – hypothesis is that two interventions are indistinguishable from
each other

11. Essential elements
• Prospective looking
• Intervention done: Prophylactic/ Diagnostic/ Therapeutic
• Control: For comparing to intervention group
• Randomization: Equality of baseline characteristics
• Blinded: To avoid systemic bias

13. Clinical trials done for
1. Drugs for prevention, treatment or palliation.
2. Clinical devices, such as intrauterine devices.
3. Surgical procedures, rehabilitation procedures.
4. Medical counselling.
5. Diet, exercise, change of other lifestyle habits.
6. Hospital services, e.g. integrated versus non-integrated, acute versus
chronic care.
7. Risk factors.
8. Communication approaches, e.g. face-to-face communication versus
pamphlets.
9. Different categories of health personnel, e.g. doctors versus nurses.
10. Treatment regimens, e.g. once-a-day dispensation versus three times a
day.

14. Clinical Drug Trials

15. Introduction
• Sample: Human
• Guidelines: Good clinical practice guidelines
• Backbone: Informed consent

16. Phases of clinical trial
• Phase 0:
• aka micro dosing trial
• 20-30 patients are given micro doses to screen the response of drugs
• Phase 1:
• On normal healthy human volunteers
• Sample size <100
• Done to calculate toxic dose
• Conducted by clinical pharmacologists
• Not done for highly toxic medicines like anti cancer drugs and immunosuppressant
• Aka safety study , toxicity study

17. • Phase 2:
• Done on patients
• Sample size 100-200
• Done to calculate therapeutic dose
• Single / double blinding done
• Conducted by clinicians
• Associated with maximum drug failure (success rate only about 33%)
• Wastage of resources (time, money, health) maybe there in case of failure
• Phase 3:
• Done on patients after success of phase 2
• Sample size >1000
• Done by clinicians to calculate therapeutic dose
• Double/Triple blinding done
• Best phase to check pharmacokinetics and dynamics

18. • Phase 4:
• Aka post marketing surveillance
• Sample – any patient consuming the drugs
• Size of sample not fixed
• Special population (pregnant, children, old) not included
• Aim: reporting of any adverse effect associated with drug, not reported so far
in earlier trial phases
• Reporting is done in pharmacovigilance department

19. Other RCTs
• Preventive trials:
• It means primary prevention.
• These trials are purported to prevent 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.

20. • Risk factor trial:
• 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.
• Cessation experiments:
• An attempt is made to evaluate the termination of a habit which is considered to be
causally related to a disease.
• Evaluation of health services:
• Randomized controlled trials have been extended to assess the effectiveness and
efficiency of health services. Often. choices have to be made between alternative
policies of health care delivery

21. Examples of clinical trial
• Scurvy trial by Dr. James Lind in 1747

22. Non Randomized Control Trial

23. Types
• Uncontrolled trials
• Natural experiments
• Before and after comparison studies

24. Advantage and Disadvantage
• Advantage:
• Scientifically ideal method
• It removes large number of biases
• It builds up faith in the findings of the study
• It ensures temporal relationship between exposure and outcome
• Disadvantage:
• Needs long time
• It has ethical issues
• Expensive
• In some random allocation of groups get difficult
• All the disadvantages of cohort studies

25. Community Trials

26. Introduction
• The main purpose is to reduce the occurrence of diseases and deaths
early in life in the whole community, hence the name.
• The experimental population is randomly selected from a country or
region and almost identical and comparable with the reference
(control) population in possessing all its characteristics.

27. WHY CIT ?
.
THE HEALTH STATUS OF
A COMMUNITY.
CHANGE TO HEALTHIER LIFESTYLE
BY HIGH-RISK GROUPS
CHANGE THE
BEHAVIOR OF OTHER MEMBERS
OF THE SOCIETY
INTERVENTIONS AIMED AND FOCUSED
AT SPECIFIC DISEASES
HEALTH ACTIVITIES
IN COMMUNITIES
THE CONFIDENCE IN THE PEOPLE
AND THEREBY THEIR INVOLVEMENT
AND ACCEPTANCE
REDUCTION IN RISK FACTORS
THE INCIDENCE OR
COURSE OF OTHER DISEASES.
IMPACT ON
LEADS
TO
AFFECT
ENHANCE

28. GENERAL OBJECTIVES
TO INCREASE HEALTH KNOWLEDGE
OF THE WHOLE COMMUNITY ,
TO DEVELOP POSITIVE AND RIGHT ATTITUDE
IN THE COMMUNITY
TO INCREASE THE PRACTICE OF POSITIVE
HEALTH BEHAVIOR OF THE WHOLE COMMUNITY
THEREBY PREVENTING EARLY DISEASES
AND DEATHS IN THE COMMUNITY
H
E
A
L
T
H
E
D
U
C
A
T
I
O
N

29. STUDY DESIGN
• QUASI - EXPERIMENTAL TYPE
• THE INVESTIGATOR WILL NOT BE HAVING AS MUCH OF A CHANCE OF
RANDOM ALLOCATION OF THE INDIVIDUALS TO THE TWO GROUPS AS IN
CLINICAL TRIALS.
• EMBEDDED DESIGN
• Embedded type will help
• In reducing secular differences
• In reducing confounding bias as the both known and unknown
variable factors will be equally distributed in both the
populations.

30. Intervention
• Idea is to bring about the attitudinal change in the people to alter their
negative life styles and to sustain.
• Modes of Intervention:
• Social cognition/learning - Change of behavior can be achieved through intensive
exposure to important models like pop stars, players.
• Reasoned action and planned behaviour - By adapting the information given by
creditable person first and sustaining it by self management later
• Persuasive communication - Through mass media like movies, television etc to
convince them to adopt positive life styles can also bring about a change in life style.
• Social marketing - Preventive health services are the products to be marketed and
the target audience, costs and benefits have to be defined.

31. PRECEDE-PROCEED MODEL INTERVENTION
•The PRECEDE process stands for Predisposing,
Reinforcing, and Enabling Constructs in Educational-
environmental Diagnosis and Evaluation and it involves
accessing the following community factor:
• Social assessment
• Epidemiological assessment
• Ecological assessment
• Match appropriate intervention
• Implementation of intervention
•PROCEED stands for Policy Regulatory and Organizational
Constructs in Educational and Environmental Development and
the process follows with implementation, process, and impact
and outcome evaluation.

32. Bias
• Bias may arise from errors of assessment of the outcome due to human
element .
• These may be from 3 sources:
• 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 – investigator measuring the outcome of a trial may be influenced if he
knows beforehand the particular therapy to which the patient 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.

33. Blinding
• In order to reduce above problems, blinding is adapted
• It can be done in 3 ways:
• Single blind trials - participant is not aware of group allocation.
• Double blind trials - neither doctor nor participant is aware of
group allocation received.
• Triple blind trials - participant, investigator and person analyzing data are
blind.

34. ANY QUESTIONS?