This document discusses different types of epidemiological study designs used to test hypotheses, including observational studies and experimental studies. It provides details on randomized controlled trials (RCTs), describing the basic steps in conducting an RCT which include developing a protocol, selecting and randomizing study populations, implementing interventions, follow up, and outcome assessment. It also discusses other types of experimental epidemiology studies like prevention trials, risk factor trials, cessation experiments, and trials evaluating health services. Non-randomized study designs are also briefly covered.

1. DR m a thaher
Pg 1st year
COMMUNITY MEDICINE 07/04/2015

2. 
“THE SMOKING OF 30-40
CIGARETTS PER DAY CAUSES
LUNG CANCER IN 10%
OFSMOKERS AFTER 20 YEARS
OF EXPOSURE”
HYPOTHESIS

3. 
EPIDEMIOLOGY
METHODS
1.OBSERVATIONAL STUDIES
A.DESCRIPTIVE B.ANALYTICAL
STUDIES STUDIES
1.ECOLOGICAL
2.CROSS-
SECTIONAL
3CASE-CONTROL
4.COHORT
HYPOTHESIS
FORMULATION TESTING
2.EXPERIMENTAL STUDIES
INTERVENTIONAL STU
A.RCT
B.FIELD TRIALS
C.COMMUNITY TRIALS
CONFORMATION

4. 
EXPERIMENTAL
EPIDEMIOLOGY
 In the 1920s,”experimental epidemiology” meant the
study of epidemics among colonies of experimental
animals such as rats and mice.in modern
usage,experimental epidemiology is often equated
with RCT.
 AIMS
To provide a scientific proof.
To provide a measuring method.

5. 
Animal studies
At the beginning of this century
,,WEBSTER(us)andTOPLEY,WILSONand
GREENWOOD(england) carried out animal
experiments.
ADVANTAGES
 Experimental animals can be bred inlab,manpulated
easily according to investigator wishes.
 Multyply rapidly

6. 
Limitations:-
 Not all the diseases reproduse in animals.
 All the conclusions derived from animal
experiments may not be strictly appicable
to human beings.
EX:-WHO trial on typoid vaccine.-Almorth Wright
RCT trials.
Animal studies

7. 
HUMAN EXPERIMENTS
 Human experiments will always be needed to
investigate disease aetiology and to evaluate the
preventive and therapeutic measures.
 These studies are even more essential in the
investigation of diseases that cannot be reproduced
in animals.
 Ex: JAMES LIND
EDWARD JENNER
GOLDBERGER’S EXPERIMENT.

8.  Although the experimental method is unquestionably
the most incisive approach to scientific problem, ethical
and Iogistic considerations often prevent its application
to the study of disease in humans.
 Therefore, before launching human experiments, the
benefits of the experiment have to be weighed against
risks involved.
 The volunteers should be made fully aware of all
possible consequences of the EXPERIMENT.
 Thus when an illness is fatal (e.g., excessive
haemorrhage) and the benefit of treatment (e.g., blood
transfusion) is self-evident, it would be ethically
unacceptable to prove or disprove the therapeutic value
of blood.

9.  However, such instances represent only a small part
of the total research effort.
 On the other hand, in the present era of scientific
medicine, many unscientific or scientifically
unsound procedures are still being carried out.
 EX;diethylstilbesteral-ca.vagina.
 The WHO in 1980 has laid down a strict code of
practice in connection with human trials.
Experimental studies are two types.
A. RCT
B. NON-RANDAMOISED.

10. 
It IS really an epidemiologic experiment.
 Since its introduction. The RCT has questioned the
validity of such widely used treatments as oral
hypoglycemic agents, varicose vein stripping,
tonsillectomy, ……etc
 For new programmes or new therapies, the RCT is
the No.1 method of evaluation.
RANDOMIZED
CONTROL TRIALS

12. Basic steps in RCT conducting:
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. It specifies:-
Aims &objectives of study
Questions to be answered
Criteria for selection of study and control groups
Size of sample
The procedures for allocation of subjects into study
and control groups.
Treatment to be applied.
Standardization of working procedures
Schedules and responsibilities of the parties
involved
1.The protocol

14. 
AIM:-
 preventing bias and to reduce the source
of errors in the study.
Preliminary test runs: some times it is useful
to have short test to run of the protocol to
see any flaws
Protocol

15. 
 REFERANCE POPULATION:-
 Population to which the findings of the trail are
expected to be applicable.
 Ex :-specific age group people
geographically limited
population of school children
SELECTING REFERENCE
&EXPERIMENTAL
POPULATION

16. 
it is derived from reference population.
It is the population that actully participates in
experimental studies.
Participants must fullfil 3 criterias….
1.must give informed consent
2.should be representative of the population.
3.should be eligible for the trail.
EXPERIMENTAL POPULATION

17. 
 it is a statistical procedure by which
participents allocated in to study and control
groups.
 it is a heart of RCT
 It is an attempt to eliminate bias and allow for
comparability.
 It will give greatest confidence that the groups are
comparable so that”like can be compared with like”.
RANDOMIZATION

18. 
 Randomization is done only after the participants
entered the study,that is after having been qualified
for the trial and has given informed consent to
participate in study.
 Randomization best done by using a table of random
numbers.(simple random sample).random numbers
are a haphazard collection of certain
numbers,arranged in a cunning manner to eliminate
personal selection of unconscious bias in taking out
the sample.
Randomization

19. 
 After selection of study& control group,intervene the
study group by deliberate application(vaccine, drug)
as laid down in protocol.
 This manipulation creates an independent varieble
(e.g. drug,vaccine)whose effect is then determined
by measurement of the final outcome,which
constitutes the dependent varieble(incidence of
disease,survival time.)
MANIPULATION

20. 
 This implies examination of the experimental &
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
final assessment of outcome.
 Attrition:-some cases losses to follow-up due to
death,migration,loss of intrest.
 If the attrition is substantial,it may be difficult to
generalise the results to refferens population.
FOLLOW-UP

21. 
 POSITIVE RESULTS:-Benefits of experiment
measurers reduced incidence or severity of
disease…..
 NEGATIVE RESULTS:-Severity and frequency of
side-effects and complications,if any,including death.
ASSESSMENT

22. 
 Bias may arise from errors of assessment of the
outcome due to human element.these may be from 3
sourses.
 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 –investigater measuring the outcome of a
trial may be influnced if he knows beforehand the
particular therapy to which the pt has
subjected.(observer variation)
BIAS

23. BLINDING:-In order to reduce above
problems,blinding is adapted .it can be done in 3
ways.
A.Single blind trials:-participant is not aware of
group allocation.
B.Double blind trials:-neither doctor nor
participant is aware of group allocation.& Rx
received.
C.Triple blind trials:-participant,investigater and
person analysing data are blind.
Third there may be bias in evaluation.-the
investigator may give subconsciously give a
favorable report of the outcome of trial.

24. 
1.Concurrent parallel study designs
2.Cross over type of study design.
STUDY DESIGNS

25. 
Concurrent parallal study
designs.

26. 
Cross over type of study
design

27. 
For the most part,”clinical trials” have been
concerned with evaluting therapeutic agents,mainly
drugs.
Eg: trials of folate- to prevent NTD.
efficacy of tronsillectomy for recurrent
throat infections.
Many ethical, administrative, & technical problems
are involved in the conduct of clinical trials.
Types of RCT-1.clinical
trials

28. 
It implies primary prevention.
Most common trials are done vaccines &
chemoprophilactic
Eg: Medical research concil of UK – woophing cough
since preventive trials involve larger number of subjects
and longer time span to obtain results,there may be
greater number of practical problems in their
organisation and execution.
2.Preventive trials

29. 
 A type of prevenive trials in which he investigator
internvenes to interrupt the usual sequence in the
development of disease for those individual who has
risk factor in developing the disease
 Often this involves risk factor modification
 Eg. CHD- 4 major risk factor- WHO study- clofibrate
therapy
 OSLO study, MRFIT in US
3.Risk factor trial

30. 
 Another type of preventive trial is ihe cessation
experiment. In this type of study, an attempt is made to
evaluate the termination of a habit (or removal of
suspectedagent) which is considered to be causally
related to a disease.
 If such action is followed by a significant reduction
in the disease, the hypothesis of cause is greatly
strengthened.
 Ex :cigarette smoking-lung cancer.
Cessetion experiments

31. 
 One of the aim of experimental etiology is to confirm
or refute etiological hypothesis.
 eg;: RLF
 Since most disease are fatal,disabling, human
experiments to conform an aetiological hypothesis
are rarely possible.
5.Trial of etiological agents

33. 
 RCT have been extended to assess the efectiveness &
efficiency of health services.
 Eg: Domicilliary treatment- pulm. Tuberculosis.
 Health services research studies.
6.Evaluaton of health
services

34. 
 Due to ethical, administrative, cost it is not always
possible to resort to RCT.
 Approach is crude. As there is no randamisation,
degree of comparability will be low and chances of
spurious results will be high.
Non Randamized Trials

35. 
 1. Uncontrolled trials:
 Trials with no comparision groups.
 Useful to known whether specific therapy is
valuable for particular disease, to determine
the appropriate dose, to investigate adverse
reaction.
 Eg:indirect epidemiological evidence that the
pap test is effective in reducing mortality from
cervical cancer.
Examples of non randamized trials

36. 
 2. Natural experiments:
 Where experimental studies are not possible in human
beings, some natural circumstances mimics as
experiment
 Eg: smokers and non smokers- lung cancer.
John snow discovery- cholera- water born disease.
Non-randomized trials

37. 
John snow’s experiment

38. 
3.BEFORE AND AFTER COMPARISON STUDIES:
These community trials fall into 2 distinct groups.
 A.Before & after comparison studies without control.
 B.Before & after comparison studies wth control
Non-Randomized trials

39. 
 These studies centre round comparing the incidence
ofdisease before and after introduction of a
preventive measure.
 The events which took place prior to the use of the
new treatment or preventive procedure are used as a
standard for comparison.
 In other words, the experiment serves as its own
control; this eliminates virtually all group
differences.
Before &after comparison
studies without control

40. Ex:James Lind –scury experiment
Prevention of polio by salk and sabin vaccine
 In order to establish evidence in before and after
comparison studies, the following are needed; (a) data
regarding the incidence of disease, before and after
introduction of a preventive measure must be
available
 (b) there should be introduction or manipulation of
only one factor or change relevant to the situation,
other factors remaining the same.
 as for example, addition of fluorine to drinking water
to prevent dental caries
 (c) diagnostic criteria of the disease should remain the
same
 (d) adoption of preventive measures should be over a
wide area
 (e) reduction in the incidence must be large following
the introduction of the preventive measure, because
there is no control.

41. 
1970 1971 %change
deaths 564 464 -17.7
injuries 14620 12454 -14.8
Effect ofadoption of compulsory seat-belt
legislation in vectoria,Aus-1971

42.  In the absence of a control group, comparison
between observations before and after the use of a
new treatment or procedure may be misleading.
 In such situations, the epidemiologist tries to utilize
a "natural" control group i.e., the one provided by
nature or natural circumstances.
 If the preventive programme is to be applied to an
entire community. he would select another
community as similar as possible, particularly with
respect to frequency and characteristics of the
disease to be prevented.
Before and after comparison studies with
control

43. 1970 1971 %change
DEATHS
Victoria 564 464 -17.7
Other states 1426 1429 0.2
INJURIES
Victoria 14620 12,454 -14.8
Other states 39,980 40,396 1.0
Effect of adaptation of compulsary seat-
belt legislation in victoria comparing
with other states(where legislation not
applied)

44. 
 Scientifically ideal method.
 Removes a large number of biases related to
selection and measurement,
 Ensures temporal relationship between exposure and
outcome.
 Builds up ‘faith ‘ in the findings of the study.
Advantages

45. 
 In many situations, rspecially those which concern
study of risk factors or prognostic factors,one can not
randomly allocate human beings into two groups.
Eg ;-smoking- lung cancer
 Ethical issues.
 Expensive
 Long time need…..
Disadvantages

46. THANK YOU