types and design of clinical trails

1. BY DINESH
M PHARM PHARMACOLOGY
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2. CONTENTS
 INTRODUCTION
 TYPES AND DESIGN
 EXPERIMENTAL STUDY
 OBSERVATIONAL STUDY
 REFERENCES
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3. INTRODUCTION
 A study design is a specific plan or protocol for
conducting the study, which allows the investigator to
translate the conceptual hypothesis into an
operational one.
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5. CONT…
 Observational: Studies that do not involve any
intervention or experiment.
 Experimental: Studies that entail manipulation of the
study factor (exposure) and randomization of subjects
to treatment (exposure) groups.
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7.  Non-experimental.
 Observational because there is no individual
intervention.
 Treatment and exposures occur in a “non-controlled”
environment.
 Individuals can be observed prospectively,
retrospectively or currently.
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9. CASE REPORTS
 Detailed presentation of a single case or handful of
cases
 Generally report a new or unique finding
 e.g. previous undescribed disease
 e.g. unexpected link between diseases
 e.g. unexpected new therapeutic effect
 e.g. adverse events
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10. CASE SERIES
 Experience of a group of patients with a similar
diagnosis.
 Cases may be identified from a single or multiple
sources.
 Generally report on new/unique condition .
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11.  Advantages
Useful for hypothesis generation
Informative for very rare disease with few
established risk factors
 Disadvantages
Cannot study cause and effect relationships
Cannot assess disease frequency
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13. ANALYTICAL STUDY
 Group data
Ecologic study
 Individual data
Cross-sectional study
Case-control study
Cohort study
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14. ECOLOGICAL STUDY
 An investigation of the distribution of health and its
determinants between groups of individuals.
 Unit of study is the aggregate data not individual
level.
 It is usually be conducted as the first step study for
research.
 The result is difficult to interpret because of
confounding and bias.
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15.  Advantages
Cheap, quick and convenient since it usually
come from existing data.
 Disadvantages
Inability to link exposure with disease in
individual (ecological fallacy)
Limit to control effect of other factors
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16. CROSS SECTIONAL STUDY
 An “observational” design that surveys exposures and
disease status at a single point of time (a cross-section
of the population)
 ADVANTAGES
Gives general description or scope of
problem.
Useful in health service evaluation and
planning.
Baseline for prospective study .
Low-cost.
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17.  DISADVANTAGES
No calculation of risk.
Temporal sequence is unclear.
Not good for rare diseases.
Selective recall can lead to bias
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18. CASE CONTROL STUDY
 An “observational” design comparing exposures in
disease cases vs. healthy controls from same
population.
 Exposure data collected retrospectively.
 Most feasible design where disease outcomes are rare.
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19. ODDS RATIO
Odds ratio= ad/bc
ADVANTAGES
Cheap, easy and quick studies
Require comparatively few subjects
DISADVANTAGES
If the incidence of exposure is high, it is difficult to
show the difference between cases and controls
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SUSPECTED
RISK FACTOR
CASE CONTROL
PRESENT A B
ABSENT C D
A+C B+D

20. COHORT STUDY
 An “observational” design comparing individuals with
a known risk factor or exposure with others without
the risk factor or exposure.
 Looking for a difference in the risk (incidence) of a
disease over time.
 One of best observational design.
 Data usually collected prospectively (some
retrospective)
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22.  ADVANTAGES
Can establish population-based incidence.
Accurate relative risk (risk ratio) estimation.
Can be used where randomization is not possible.
 DISADVANTAGES
Lengthy and expensive.
May require large samples.
Not suitable for rare diseases.
Not suitable for diseases with longlatency
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24.  Treatment and exposures occur in a “controlled”
environment.
 Planned research designs.
 Clinical trials are the most well known experimental
design.
 Investigator can “control” the exposure akin to
laboratory experiments except living populations are the
subjects.
 Generally involves random assignment to groups.
 The ultimate step in testing causal hypotheses
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25. RANDOMIZED CONTROLLED TRIAL
 A design with subjects randomly assigned to
“treatment” and “comparison” groups.
 Provides most convincing evidence of relationship
between exposure and effect.
 Not possible to use RCTs to test effects of exposures
that are expected to be harmful for ethical reasons.
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26. The basic steps include the following:
• Drawing up ‘Protocol’
• Selection of Reference and Experimental Population.
• Randomization
• Manipulation or Intervention
• Follow-up
• Assessment of outcome
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29.  ADVANTAGES
Ability to randomize subjects.
Temporal sequence of cause and effect.
Can control extraneous variables.
Best evidence of causality
 DISADAVANTAGES
Expensive.
It may be unethical to assign persons to certain
treatment or comparison groups
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30.  Other Types of Experimental Study
Field trials
 Community trials
 Animal studies
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31. Non-Randomized Trials
 Also known as Quasi-Experimental Designs.
 It is a type of research in which the investigator manipulates the
study factor but does not assign individual subjects randomly to
the exposed & non- exposed groups.
 These are designed as:
• It is always not possible for ethical, administrative and
other reasons to resort to a RCT.
• Some preventive measures apply only to groups or
community-wide basis.
• When disease RCT require follow-up of thousands of
people for a decade or more.
• As here randomization is not done. So, low comparability than
RCT and chances of spurious results are high than RCT.
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32.  These studies may be of following types:
 Uncontrolled Trials
 Natural Experiments
Before and after comparison studies
• With control
• Without control
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33. META ANALYSIS
 Meta-analysis is a statistical analysis of a collection of
studies.
 Meta-analysis methods focus on contrasting and
comparing results from different studies in
anticipation of identifying consistent patterns and
sources of disagreements among these results.
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34. REFERENCES
 Epidemiology by Leon Gordis, 5th Edition
• Textbook of Public Health and Community Medicine by
Rajvir Bhalwar
• Park’s Textbook of Preventive and Social Medicine by K.
Park, 23rd Edition
• Jekel’s Epidemiology, Biostatistics, Preventive Medicine,
and Public Health by David L Katz et al, 4th Edition
• Health Research Methodology : A Guide for Training in
Research Methods, 2nd Edition
• Basic Epidemiology by R Bonita
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