EXPERIMENTAL EPIDEMIOLOGY

2. RANDOMIZED
CONTROLLED
TRIALS (RCT)
NISHATH NIHAR
FINAL YEAR

3.  CONTENTS:
Introduction
History
Definition
Steps in RCT
Blinding
Types of RCT
Advantages and Disadvantages
Uses
Conclusion
References

4.  INTRODUCTION
 In the last 35-40 years, determined efforts have been made
to use scientific techniques to evaluate methods of
treatment & prevention.
 An important advance in this field is the development of
RANDOMIZED CONTROLLED TRIALS

5. HISTORY
 In 1747, James Lind performed a human experiment in
which he added different substances to diet of 12
soldiers suffering from SCURVY
 Oranges & lemons, cider, vinegar, sulphuric acid, salt
water and garlic
 Only the sailors given oranges & lemons recovered

6. DEFINITION
“ An epidemiological experiment in which subjects in
a population are randomly allocated into groups,
usually called study and control groups to receive and
not receive an experimental preventive or therapeutic
procedure, maneuver or intervention”
-John M Last,2001

7. STEPS IN RCT
1. Drawing up a protocol
2. Selecting reference and experimental population
3. Randomization
4. Manipulation
5. Follow up
6. Assessment of outcome

8. 1. DRAWING UP A PROTOCOL
• The protocol specifies the aims & objectives of the
study
• Criteria for selection, size of sample, procedures for
allocation of study & control groups
• Standardization of working procedure, schedules &
responsibility of people involved in trial
• The protocol should be strictly adhered to throughout
the study

9. 2. SELECTING REFERENCE AND EXPERIMENTAL
POPULATION
• Reference or target population: population to which the
findings of trial, if found successful are expected to be
applicable(eg, drug vaccine )
• Experimental or study population: Actual population that
participates in trials
• Randomly chosen from reference population
 Criteria- must give informed consent
- belong to reference population
- eligible for the trial

10. 3. RANDOMIZATION
 Statistical procedure by which participants are allocated into
study & control groups, to receive or not to receive an
experimental preventive or therapeutic procedure
 It is done to eliminate “Bias” and allows comparability
 Individual gets an equal chance of being allocated into either
group

11.  Randomization is best done using a “ Table of
random numbers”

12. 4. MANIPULATION
 Deliberate application or withdrawal or reduction of the
suspected casual factor( eg., drug vaccine , dietary component,
habit etc) as laid down in the protocol
 It creates an Independent variable.

13. 5. FOLLOW UP
 Examination of experimental and control group subjects at
defined intervals of time, in a standard manner under the
same given circumstances till final assessment of outcome.
 ATTRITION: Some loses to follow up are inevitable due to
factors like death, migration or loss of interest

14. 6. ASSESSMENT
 POSITIVE RESULTS: Benefits such as reduced incidence or
severity of disease
 NEGATIVE RESULTS: severity and frequency of side effects,
complications , including death
 BIAS
a) Subject variation
b) Observer bias
c) Evaluation bias
 Eliminated by “ BLINDING”

16. BLINDING
• Done to eliminate bias
• Single blind trial- participant is not aware whether he belongs
to study or control group

18. DOUBLE BLIND TRIAL
 Neither the participant nor the investigator is aware
TRIPLE BLIND TRIAL
The participant, investigator and person analyzing data all are
Blind

19. TYPES IN RCT
A.CLINICAL TRIALS: It is done various purposes like
prophylactic trials (e.g immunization, contraception)
therapeutic trials(e.g drug treatment, surgery)
safety trials(eg side effects of Ocs)
B. PREVENTIVE TRIALS: Synonymous with primary
prevention.
e.g vaccine trials
analysis must result in clear statement about risk involved,
benefits to community, cost etc

20. C. RISK FACTOR TRIALS: Investigator intervenes to interrupt the
usual sequence in the development of disease for individuals
who have risk factor for developing a disease
eg. Reduction in blood cholesterol, control of BP in
preventing CHD.
D. CESSATION EXPERIMENTS: Attempt is made to evaluate the
termination of a habit which is considered to be casually related
to disease
eg. Smoking and lung cancer

21. E. TRIAL OF ETIOLOGICAL AGENTS: it is done to confirm or
refute an etiological hypothesis.
F. EVALUATION OF HEALTH SERVICES: Efficiency & effectiveness
of treatment
Eg in India domiciliary treatment of pulmonary TB was as
effective as costlier hospital treatment.

22. ADVANTAGES:
• Eliminates bias
• Facilitates blinding
• Results in evidence-based medicine
DISADVANTAGES:
• Time and cost
• Ethical issues

23. USES
 Community diagnosis
 Evaluation of health services
 Evaluation of individual risk
 Searching for causes and risk factors
 Syndrome identification

24. CONCLUSION
 RCT’s are the best way to test the safety and efficacy of new
treatment
 They are regarded as the “GOLD STANDARD” of clinical
testing in new medical interventions.

25. REFERENCES
• K.PARK Textbook of preventive & social medicine, 22nd
edition
• SOBEN PETER, Essentials of public health dentistry, 5th
edition
• Wikipedia

26. THANK YOU