Basics of experimental epidemiology. Useful for taking lecture classes.

1. EXPERIMENTAL EPIDEMIOLOGY

3. HIERARCHY
OF EVIDENCE

4. INTRODUCTION
An experiment is:
 the final or definitive step in the research process,
 a mechanism for confirming or rejecting the validity of ideas, assumptions
and hypothesis.
The Randomized Controlled Trial (RCT) is the most scientifically
rigorous method of hypothesis testing available
GOLD STANDARD TRIAL
evaluating the effectiveness of interventions

5. AIMS
To provide:
 "scientific proof" of etiological factors.
 A method of measuring the effectiveness and efficiency of health services.
EXPERIMENTAL
EPIDEMIOLOGY
ANIMAL
STUDIES
HUMAN
EXPERIMENTS

6. HUMAN EXPERIMENTS
Human experiments will always be needed to investigate disease
aetiology and to evaluate the preventive and therapeutic
measures.
History:
James Lind (1747): Study on scurvy

8. CLASSIFICATION
Randomized controlled trials
• those involving a process of random allocation
Non – randomized trials
• those departing from strict randomization for
practical purposes, but in such a manner that non-
randomization does not seriously affect the
theoretical basis of conclusions.

9. RANDOMIZED
CONTROLLED TRIALS
(RCT’s)

10. Essential elements of a clinical trial
1. Prospective
Subjects followed forward
2. Intervention
Prophylactic, diagnostic or therapeutic
3. Control
Compared to intervention group
4. Randomized
Equality of baseline characteristics
5. Blinded
Systematic bias

11. Structure of a clinical trial

12. Steps in clinical trial
1. Drawing up a protocol
2. Selecting reference and experimental populations
3. Randomization
4. Manipulation or intervention
5. Follow-up
6. Assessment of outcome

13. THE PROTOCOL
The aims and objectives
Questions to be answered
Criteria for the selection of study and control groups
Size of the sample,
Procedures for allocation of subjects
Treatments to be applied
Standardization of working procedures
Schedules
Responsibilities of the parties

14. Clinical trial question
Type of research question determines the trial design
For a research question addressing an intervention:
P • POPULATION
I • INTERVENTION
C • COMPARISON
O • OUTCOME
T • TIME

15. For adult patients, will the use of a powered toothbrush, compared to a
manual toothbrush, result in reduction in plaque and/or gingivitis?
P I
C O
TRY THIS

16. SELECTING REFERENCE AND
EXPERIMENTAL POPULATIONS
REFERENCE OR TARGET POPULATION:
It is the population to which the findings of the trial, if found successful, are
expected to be applicable.
EXPERIMENTAL OR STUDY POPULATION
The study population is derived from the reference population, on which the
study is conducted..

17. RANDOMIZATION
Of a clinical trial

20. PREDICTABILITY
The critical element of randomization is the
unpredictability of the next assignment

21. RANDOMIZATION
Randomization is a statistical procedure by which the
participants are allocated into groups usually called “study” and
“control” groups.
Elimination of “selection bias”
Three common randomization schemes
Simple Randomization
Stratified Randomization
Cluster Randomization

22. Randomization
Objective of randomization
 Everyone in the study has an equal probability of being
offered each intervention
 All prognostic variables, known and unknown, have an
equal distribution in the treatment groups in the long run

23. Methods of randomization
Simple randomization

24. Stratified randomization

25. Clustered randomization

26. MANIPULATION
The next step is to intervene or manipulate the study
(experimental) group by the deliberate application or
withdrawal or reduction of the suspected causal factor or
drug or treatment.

27. FOLLOW-UP
This implies examination of the experimental
and control groups:
at defined intervals of time,
in a standard manner, with equal intensity,
under the same given circumstances,
in the same time frame till final assessment
of outcome.

28. ASSESSMENT
The final step is assessment of the outcome of the trial in terms of-
Positive results- reduced incidence or severity of the disease,
cost to the health service or other appropriate outcome.
Negative results- severity and frequency of side-effects and
complications.
The incidence of positive/negative results is rigorously compared in
both the groups.

29. BIAS IN CLINICAL TRIALS
Bias may arise from errors of assessment of the outcome due to human
element-
SUBJECT VARIATION
OBSERVER BIAS
EVALUATION BIAS

30. BLINDING/MASKING
It is the procedure of keeping the knowledge of intervention assignment away
from those directly involved in the trial.
Ensures that the outcome is assessed objectively.
Can be done in three ways-
Single Blind Trial
Double Blind Trial
Triple Blind Trial

32. BASIC DESIGNS OF CLINICAL
TRIALS
Basic two-arm parallel design
Cross over design
Factorial design

34. PHASES OF CLINICAL TRIAL

35. Types of clinical trials
Effectiveness: Examine the outcomes of interventions under circumstances
that more closely approximate the real world
Efficacy: Investigates the benefits of an intervention under ideal and highly
controlled conditions

36. Other types of clinical trials . . .
Preventive trials
Risk factor trials
Cessation experiments
Evaluation of health services
Field trials
Community trials

37. NON-RANDOMIZED TRIALS
• It is undertaken when:
• Not feasible to conduct RCT
• Secondly, some preventive measures can be applied only to groups or on a
community-wide basis.
• Thirdly when natural history of disease is long

38. Examples of non-randomized trials
Uncontrolled trials
Natural experiments
Before and after studies

39. ADVANTAGES
•Safety: relatively few individuals exposed to unpredicted risks in untried
interventions.
•Vigour : capable of critical tests of limits of applicability.
•Precision: theorized causal factor can be defined and limited exposure of test
factor under control of researcher.
•Efficiency: relatively few observations needed to refute some hypothesis.
•Assumptions: random allotment of treatments is assured by the design.

40. DISADVANTAGES
Impracticality: inborn attributes cannot be manipulated.
Predicted risk of intervention is great. Long term observation is
difficult. Large number of subjects needs to detect small
differences.
Reductionism: focus on one independent variable excludes
others from attention.
Representativeness: difficult to recruit a truly random sample
from ‘universe’.
Expense: relatively great in staff and logistics
Public acceptance: undue suspicion of outcomes.

41. Summary
Hierarchy of evidence
Aims of experimental epidemiology
Classification of experimental studies
Randomized controlled trials
1. Structure
2. Steps
3. Blinding
4. Basic designs
5. Phases
Non-randomized trials
Advantages
Disadvantages

42. References and suggested reading
PARK K. PARK’S TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE.
21st ed. Jabalpur: Banarsidas Bhanot; 2011.
Soben Peter. Essentials of Preventive and Community Dentistry. 4th ed.
Kendall JM. Designing a research project: randomised controlled trials and their
principles. Emerg Med J. 2003 Mar 1;20(2):164–8.