Experimental Epidemiology

Dr Forhad A Zaman
 Experimental Epidemiology
• Comes after descriptive & analytical type & more
convincing
• In small set up (hospital/ lab) – clinical trials
while in community – interventions (Field trials)
• Similar to cohort in design except - power of
intervention is with investigator

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 Experimental Epidemiology
1. Random representative sample drawn (study
Population) from Reference population
2. Excludes all who at the commencement have
a) Outcome of interest
b) Exposure of interest
3. These persons (without exposure & outcome) are
randomly allocated to two sub groups
4. Now
a) One group is given exposure
b) Other nil or placebo

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 Experimental Epidemiology
5. 2 groups are followed for time to see the
occurrence of outcomes
6. Rates are calculated for O + in both groups to
see the association between E & O.
Example :
Role of INH chemo prophylaxis in prevention of
tuberculosis amongst contacts of open cases of
tuberculosis
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 Exp Epidemiology

Special issues
They have all advantages/ disadvantages of
prospective cohort studies with three additional
problem areas of
– Costing
– Ethical considerations
– Feasibility to execute

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 Exp Epidemiology

Advantages
1. Random allocation ensures comparability in two
groups
2. Selection by investigator ensures O - & E – in both
groups
3. Dev. Of cases (O +) in groups with E – ensures
temporality
4. Noting of E – or + by investigator at start rules out
recall bias 6
 Exp Epidemiology

Types
Based on study subjects
1. Human trials
2. Animal trials
Based on study design
3. Non randomized /Randomized trials
4. Controlled trials/Non controlled trials
5. RCT

Randomized Control Trials (RCTs) are best 7

 Exp Epidemiology

Animal trials: To study

1. Body structure & functions
2. Immunological response
3. By experimentally producing the disease to
study
a) Causation
b) Pathological changes
c) Efficacy of preventive (vaccine)/ therapeutic
(drug) intervention

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 Exp Epidemiology

Animal trials: Adv/ Disadvantages

Advantages
• Can be bred in lab as per needs
• Large number & small life spawn
• Compliance
• Less ethical issues – can be sacrificed
• Done as precursor of human trials
Disadvantages
• Replicability (?)
• Extrapolation (??)
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 Exp Epidemiology
Human Trials
• Provide for ultimate evidence (superior to animal trials) –
• Essential where the disease cannot be reproduced in
animals
But
• Poses more ethical problems – written informed consent
• Compliance (human behavior)
• Number & life span cannot be influenced
Therefore
• When starting a new therapy - Benefits to be checked
against risks -

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 Exp Epidemiology
Steps under Randomized control Trials (RCT)
1. Designing protocol
1. Before starting study & no change thereafter,
2. Details of objectives,
3. selection criteria & allocation procedure,
4. Indicators for assessment
5. Pilot testing
2. Selecting study population
1. Reference/ target population
2. Inclusion/ exclusion criteria – consent, participant
bias

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 Exp Epidemiology
Steps under Randomized control Trials (RCT)
3. Random allocation to both groups
1. Eliminate selection bias & ensure comparability –
lacks in analytical studies – compensated by
matching
4. Intervention in exp group
1. Deliberate application or withdrawal of a factor
(causative/ preventive / therapeutic ONLY in exp
group
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 Exp Epidemiology
Steps under Randomized control Trials (RCT)

5. Assessment for
1. Positive (cure/ reduction in severity/ complications/
non occurrence) results
2. Negative (side effects frequency & severity)
3. Comparison in 2 groups with stat tests

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Level of errors (bias)
1. Selection bias (no as taken care by Randomization)
2. Participant bias – courtesy bias (Participant feel better
as being under treatment)
3. Observer’s bias (observer knows beforehand the
allocations)
First one is dealt by random allocation while other two
errors cannot be handled by this.
Other two are addressed by
 Single Blinding – Participant not aware of the group
 Double – neither participant nor observers
 Triple Blinding for analysis purpose
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 Exp Epidemiology
RCT - Design
Reference/ target population

Sampling – study population

Do exclusion - Not eligible & Unwilling

Randomization

Exp Group Control Group

Intervention & Follow up

Assessment
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Non Randomized trials
1. Uncontrolled trials – initial approach
Benefit of Pep’s test in Ca cervix
2. Natural experiments (cohort design) Earthquake,
Nuclear explosions, Broad street epidemic
3. Before & after (without controls) where before
serves its own control
4. Before & after with control it provides more
convincing information.

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In 1970, compulsory seat belt legislation was introduced
in ONLY Victoria state of Australia
Before & after without controls
1970 1971 % change
Death 564 464 - 17.7
Injuries 14620 12454 -14.8
Before & after with controls
1970 1971 % change
Death
Victoria 564 464 -17
Other states 1426 1429 -0.2.7
Injuries
Victoria 14620 12454 -14.8
Other states 39980 40396 1.0
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