Gives an overview of observational analytical and experimental studies

1. Achyut Raj Pandey
Research Officer
Nepal Health Research Council1
Observational Analytical
and
Experimental Studies

2. • Observational Analytical studies
• Cohort study
• Case control study
• Experimental studies
• Clinical and preventive trials
• Pre, quasi and true experimental studies
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3. Concept of cohort
The word cohort is derived from the Latin
“cohorts” meaning an enclosure, company, or
crowd.
In Roman times a cohort was a body of 300–600
infantry.
In epidemiological terms the cohort is a group of
people with something in common, usually an
exposure or involvement in a defined
population group.
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4. Definition
• Cohort study is a type of analytical study
which is undertaken to obtain additional
evidence to refute or support existence of
association between suspected cause and
diseases.
• Other names of cohort study are
Longitudinal study, Incidence study and
forward looking study
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5. Features of cohort studies
• Cohorts are identified prior to appearance
of disease under investigation
• The study groups are observed over a
period of time to determine the frequency
of disease among them
• The study proceeds from cause to effects
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6. Indications for cohort study
• There is good evidence of an association
between exposure and disease, from other
studies.
• Exposure is rare.
• Attrition of study population can be minimized.
• Sufficient fund is available.
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7. Framework of cohort study
Cohort
population
Exposed
Diseased
Non-
diseased
Unexposed
Diseased
Non-
diseased
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8. Design of Cohort Study
Then
(a+b) is called study cohort and (c+d) is called control cohort
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9. Consideration during selection of
Cohort
• The cohort must be free from disease under study.
• Insofar as the knowledge permits, both the groups
should be equally susceptible to disease under study.
• Both the groups must be comparable in respect of all
variable which influence the occurrence of disease
• Diagnostic and eligibility criteria of the disease must
be defined beforehand.
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10. Types of cohort study
• Prospective study
• Retrospective cohort study
• Ambi-directional cohort study
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11. Prospective cohort study
• The common strategy of cohort studies is to
start with a reference population (or a
representative sample thereof), some of whom
have certain characteristics or attributes
relevant to the study (exposed group), with
others who do not have those characteristics
(unexposed group).
• Both groups should, at the outset of the study,
be free from the condition under consideration.
Both groups are then observed over a specified
period to find out the risk each group has of
developing the condition(s) of interest.
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12. Example of Prospective Cohort Study
Framingham Heart Study Framework
• Initiated in 1948 to study the
relationship of a variety of factors
to the subsequent development
of heart disease with 5127
samples( 30 to 59 yrs ) at
Framingham.
• Study subjects were examined
every 2 yrs for 20 years.
• Daily Surveillance of
hospitalization at Framingham
hospital.
• Study found that Hypertensive,
tobacco smoking, elevated blood
cholesterol are associated to CHD
• Increased physical activity
associated with decreased risk of
CHD
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13. Problem of prospective study
• Study might take long duration.
• Sufficient amount of funding for long
period.
• Missing of study subjects.
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14. Retrospective Cohort Study
• A retrospective cohort study is one in which
the outcome have all occurred before the start
of investigation.
• Investigator goes back to the past to select
study group from existing records of the past
employment, medical and other records and
traces them forward through time from the
past date fixed on the records usually to the
present.
• Known with the name of Historical Cohort and
noncurrent cohort
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15. Example of Retrospective Study
• Suppose that we began our
study on association between
smoking habit and lung cancer
in 2008
• Now we find that an old roster
of elementary schoolchildren
from 1988 is available in our
community, and that they had
been surveyed regarding their
smoking habits in 1998.
• Using these data resources in
2008, we can begin to
determine who in this
population has developed lung
cancer and who has not.
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16. Ambi-directional cohort Study
• Elements of prospective and retrospective
cohort are combined.
• The Cohort is identified from past records and
assesses of date for the outcome. The same
cohort is the followed up prospectively into
future for the further assessment of outcome
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17. Steps of Cohort Study
1 •Selection of study population
2 •Obtaining Data on exposure
3 •Selection of comparison group
4 •Follow up
5 •Analysis
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18. Advantage of Cohort Studies
• Multiple outcomes can be measured for
any one exposure.
• Temporality can be established
• Suitable for new/unusual or rare
exposures.
• Can measure incidence and prevalence
• Provide direct estimate of risk.
• Less chance of bias.
• Strongest analytical capacity (among
analytical studies) 18

19. Disadvantage of Cohort Studies
• Costly and time consuming.
• Large sample size is required.
• High chances of drop out.
• Prone to confounding.
• Being in the study may alter participant's behavior.
• Not suitable for a rare disease.
• Classification of individuals (exposure or outcome
status) can be affected by changes in diagnostic
procedures.
• May arise ethical issues.
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20. • A study that compares
two groups of people:
those with the disease
or condition under
study (cases) and a very
similar group of people
who do not have the
disease or condition
(controls).
Case control study

21. – A case control study involves two populations –
cases and controls and has three distinct features
:
• Both exposure and outcome have occurred before the
start of the study.
• The study proceeds backwards from effect to cause.
• It uses a control or comparison group to support or
refute an inference.
Case control study

22. • Case : A person in the population or study
group identified as having the particular
disease, health disorder or condition under
investigation.
• Control: Person or persons in a comparison
group that differs, in disease experience (or
other health related outcome) in not having
the outcome being studied.

23. Design of Case Control Study
The investigator selects
cases with the disease
and appropriate
controls without the disease
and obtains
data regarding past exposure
to possible etiologic factors in both
groups.
The investigator then compares the
frequency of exposure of the two groups.

24. Design of Case Control Study
• Hallmark of Case Control Study: Starts from
cases and controls and searches for exposure.
Disease No Disease
“CASES” “CONTROLS”
Not ExposedExposed Exposed Not Exposed

25. – Matching is defined as the process of selecting
controls so that they are similar to cases in certain
characteristics such as age, sex, race,
socioeconomic status and occupation. (Epidemiology;
Leon Gordis, 2004)
Matching

26. – Matching variables (e.g. age), and matching criteria (e.g.
within the same 5 year age group) must be set up in
advance.
– Controls can be individually matched (most common) or
Frequency matched.
• Individual matching (Matched pairs): search for one
(or more) controls who have the required matching
criteria, paired (triplet) matching is when there is
one (two) control (s) individually matched to each
cases.
• Group matching (Frequency matching): select a
population of controls such that the overall
characteristics of the case, e.g. if 15% cases are
under age 20, 15% of the controls are also.
Matching

27. – Avoid over-matching, match only on factors
KNOWN to be cause of the disease.
– Obtain power by matching more than one control
per case. In general, N of controls should be ≤ 4,
because there is no further gain of power above that.
– Obtain generalizability by matching by matching
more than one type of control.
Matching

28. Disadvantages
• Difficulty to select appropriate controls.
• Do not establish risk or rate (only odds
ratio)
• More chance of bias
(selection/information/measurement)
• Impossible to calculate incidence rate and
attributable risk
• Not good for evaluating diagnostic tests

29. Advantages
1. Only realistic study design for uncovering
etiology in rare diseases
2. Important in understanding new diseases
3. Commonly used in outbreaks investigation
4. Useful if inducing period is long
5. Relatively inexpensive
6. Rapid and inexpensive (compared to cohort)
7. Multiple risk factors could be known.

30. Nested case-control studies
• A case-control study nested within a cohort study.
• Ideal for predictor variables that are expensive to
measure and that can be assessed at the end of the
study on subjects who develop the outcome during the
study (cases) and on a sample of those who do not
(controls).
• Because the number of cases is probably fairly small,
can match multiple controls to a given case to increase
the power.

31. Why use a nested case-control study?
• Removes recall bias because data collected
before development of disease.
• Allows for the time element to be included in
the case-control.
• Often more cost-effective than a cohort. Not
all samples collected are tested. Rather they
are stored until the disease has developed at
which time analysis begins.

32. 1. Possibility of recall bias is eliminated, since data
on exposure are obtained before disease
develops.
2. Exposure data are more likely to represent the
pre-illness state since they are obtained years
before clinical illness is diagnosed.
3. Costs are reduced compared to those of a
prospective study, since laboratory tests need to
be done only on specimens from subjects who are
later chosen as cases or as controls.
Advantages

33. Experimental study
Investigators intervene
in the natural history by
actively altering one of
the variables and then
making inference on the
relationship between
variables based on the
outcomes.

34. History
• First experimental study was conducted in 1747
by James Lind among patients suffering from
Scurvy by giving oranges and lemons to one
group, elixir vitriol to one group and cider to one
group. The group which had given oranges and
lemons recovered from scurvy but interestingly
the result was unaccepted at that time. Only 47
years later, British Admiralty permitted him to
repeat the study.

35. Experimental study can evaluate
• New drugs and new treatment of diseases
• New medical and health care technology
• New methods of primary prevention
• New program for screening
• New ways of organizing and delivering health
services
• New community health programs
• New behavioral intervention programs

36. Types
• Pre-experimental: There is manipulation of
variable but does not have control group.
• Quasi-experimental study: There is
manipulation of certain variable and has
control group but no randomization.
• True experimental design: Three features:
Randomization, manipulation and control
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37. Comparison groups in an
experimental study(trial)
• Therapy vs no Therapy
• Therapy vs Placebo
• Therapy A vs Therapy B

38. Types of Trial
Therapeutic (clinical
Trial)
• Study population
– Patients with disease
• Objectives
– Cure patients
– Prevent recurrence of
disease/risk of death
Preventive (community
Trial)
• Study Population
– Population at risk
• Objectives
– Reduce the risk of
developing disease

39. Preventive trials
• Prevention trials involve tests to find ways
to prevent particular medical conditions
or if people have them already, to prevent
them from reoccurring.
• The emphasis of these studies might be
on medicines, vitamins and minerals or
lifestyle changes.
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40. Clinical trial
• Clinical trials are research studies that explore
whether a medical strategy, treatment, or
device is safe and effective for humans.
• These studies also may show which medical
approaches work best for certain illnesses or
groups of people.
• Clinical trials produce the best data available
for health care decision making.
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41. Randomized Controlled Trial
• The randomized controlled trial (RCT) is one of
the simplest, most powerful, and
revolutionary tools of research. In essence,
the RCT is a study in which people are
allocated ‘at random’ to receive one of several
interventions
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42. Advantages of Experimental study
1. Best Results
2. Determine Cause and Effect
3. Variables Are Controlled
4. Easily Replicated
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43. Disadvantages of experimental study
1. Costly
2. Methodologically demanding
3. Not Real Life Situations
4. Human Errors
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