Types of Research Studies

Architecture of Clinical Research

 Types of Research Studies
Architecture of Clinical Research

Learning Objectives
• Be familiar with the types of research
study designs
• Be aware of the advantages,
disadvantages, and uses of the various
research design types
• Recognize a study design from published
study abstracts used as a class exercise
 Studies in Medical Literature
• Two main categories:
1. Observational:
• Studies in which subjects are observed
2. Experimental:
• Studies in which the effect of an intervention is
observed
 Observational Studies
• Case Series
• Case-Control
• Cross Sectional
• Cohort
 Observational Studies
• Case Series
– What are they?
• Author describes some interesting or intriguing
observations that occurred to a small number of patients
– Characteristics:
• The simplest design
• Descriptive
• Lead to hypotheses subsequently investigated by other
types (Case-Control, Cross-Sectional or Cohort study)
• Generally over short period of time
• Generally no controls
Case Series & Case Reports
 Observational Studies
• Case-Control
– Retrospective
– Question answered: “What happened?”
– Matching needed for controls
– Might be difficult to differentiate from Case
Series (Both are after the fact)
• Ask if the goal was to describe a phenomenon, if
description is the goal  Case Series
Case Control Studies
Case-control Studies: research in reverse

Example: association between smoking and lung cancer.

People with lung cancer are enrolled to form the case group, and people without lung cancer
are identified as controls.
Researchers then look back in time to ascertain each person's exposure status (smoking history),
(retrospective design). Investigators compare the frequency of smoking exposure in the case group
with that in the control group, and calculate a measure of association.
 Case-control study design
Exposure Disease Observer

?
Choose groups with and without disease, look
back at what different exposures they may have
had
 Observational Studies
• Cross Sectional
– AKA Surveys, epidemiologic or prevalence
studies
– What are they?
• Analyzes data collected on a group of subjects at
one time
– Question answered: “What is happening
now?”
– Short time
 Cross Sectional (cont’ed)
• Possible uses of Cross Sectional studies:
– Diagnosing or staging a disease
– Evaluating different methods of doing the same thing
• e.g. Examining the relationship between histology slides and
MRI findings of diseased carotid arteries
– Establishing norms
• e.g. Establishing normal lab values from normal subjects
– Surveys
• May use preexisting validated surveys
• To learn what people think
• Sometimes combined with interviews
 Observational Studies
• Cohort
– Question answered: “what will happen?”
– Prospective/forward
– e.g. Framingham study of cardiovascular disease:
Started in 1948, 6000 citizens participated, followed
for 20 years (study in 1970 by Gordon and Kannel)
– Possible uses:
• Typical cohort study
• Outcome assessment (patient outcomes: economic,
functional, satisfaction, QOL, ..)
• Historical Cohort studies/AKA Retrospective cohort: Relies
on prospective records collected (If accurate) – still
forward in time in the past
Cohort Studies
 Cohort studies: marching
towards outcomes

Lancet 2002; 359: 341-45

The defining characteristic of all cohort studies is that they track people forward in
time from exposure to outcome. Data collection may be prospective or
retrospective. Ex. Contraceptives and DVT.
 Cohort study design
(Prospective)
Exposure Observer Disease

Start with two groups of people who are exposed

and unexposed, follow them to see who gets
disease.
Both Cohort and Case-Control
studies are called

“Longitudinal Studies”
Notion of time
 Observational Studies

Case Series Case-Control Cohort Cross Sectional

Longitudinal Studies
 Experimental Studies
• AKA Clinical Trials (Involve humans)
• Easier to identify (usually explicitly stated
in the abstract)
• Two main categories of clinical trials:
1. Controlled trials
2. Uncontrolled trials
 Experimental Studies
Controlled trials
– Experimental drug or procedure
compared with another, with a placebo,
or with the standard procedure
– Greater validity
 Experimental Studies
Controlled Trials
• Trials with independent
concurrent controls
– Double or single blind
– Best is randomized
assignment
– Same point in time
– These include:
• RCT:
– The epitome of all research
designs
– Provides the strongest
evidence of concluding
causation
– Best insurance that results
are due to the intervention
• Nonrandomized trials:
– Assignment not randomized
– Opened to biases
• Trials with self controls
– Subject to bias (Hawthorne
effect)
– Can do crossover study (with
washout period in between)
• Trials with external control
– Uses the results of another
investigator’s research as a
comparison
– Historical controls can also be
used: for disease with no
cures yet
Randomized Controlled Studies
The Double Blind Method
 Experimental Studies
Uncontrolled trials
• Investigator’s experience with the new
drug or procedure is described but not
formally compared with another one
• More likely to be used for interventions
that are procedures rather than drug
 Experimental Studies

Controlled trials Uncontrolled trials

Self controls Independent External controls

concurrent
controls

RCT Non-randomized
Systematic Reviews &Meta-
analyses
RCT RCT
SYSTEMATIC
REVIEW
Meta-analysis
RCT RCT

“STRONGER” EVIDENCE
Study Pyramid
Best

Worst
 Classification of types of clinical research

Lancet 2002; 359: 57-61

 Temporal direction of study
designs

Lancet 2002; 359: 57-61

Advantages & Disadvantages
 Clinical Trials
• Advantages:
– RCT is the gold standard or reference
• Disadvantages:
– Expensive
– Long duration
 Cohort Studies
• Advantages:
– Design of choice for studying cause of a
disease, course, risk factors
• Disadvantages:
– Cannot be used to prove causation
– Long studies can be costly
– Vulnerable to patient attrition, migration
 Case-Control Studies
• Advantages:
– Quickest
– Least expensive
– Good for rare diseases and diseases that take long
time
– Good for investigation of a preliminary hypothesis
– Time factor research
• Disadvantages:
– Large biases
– Difficult to find matching controls
 Cross Sectional Studies
• Advantages:
– Best for:
• Determining status quo of a disease
• Prevalence of disease
• Evaluation of diagnostic procedures
– Relatively quick and inexpensive
• Disadvantages:
– Provide only a snapshot in time
 Case Series
• Advantages:
– Easy to write
– May be extremely useful to investigators
looking for causes of the observation
• Disadvantages:
– Subject to many biases in patient
selection
– Should be viewed as hypothesis
generating, not conclusive