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Observation or experiment?
Observational – cross sectional, case series, case-control studies,
cohort studies
 identify participants
 observe and record characteristics
 look for associations
Experimental – before and after studies, comparative trials
(randomized controlled clinical trials)
 identify participants
 place in common context
 intervene
 observe/evaluate effects of intervention
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Cross-Sectional Surveys
 Study is conducted at a single point in time
 Undertaken to determine for example, prevalence of risk
factors or the number of cases of a particular disease
 Major disadvantage is that such a design represents but a
single point in time , thus difficult to establish a temporal
relationship.
 Example: Gather data on exposure and disease
Sample of Population
Obese adults
prevalence of
Hypertension
Non-obese adults
prevalence of
hypertension
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Cohort Studies
 Cohorts are clearly identified groups sharing a
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common characteristics and observed over time.
Cohort studies begin with a group of people (cohort)
free of disease
Persons are chosen specifically because they were and
were not exposed to one or more risk factors
Once selected, persons are followed over time to see if
the development of new cases of the disease (or other
outcome) differs between the groups with and
without exposure.
Can be prospective or retrospective
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Case-Control Studies
 Groups are defined as having the disease or not having
the disease but controls are often matched with cases on
key fact factors
 A case-control study begins with the selection of cases
(people with a disease) and controls (people without the
disease).
 Case and control groups are compared as to frequency of
past exposure to possible risk factors; good with rare
diseases
 Similar to the cross-sectional study in that the researchers
learn about the current disease state and any risk factors
that may have existed
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Randomized Controlled (Clinical) Trial
(RCT)
 Thought to be the gold standard of all research
designs
 Have gained tremendous popularity
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Characteristics of the RCT
 Recruit many people/subjects
 Multi-centered
 Highly inclusive protocols
 Unambiguous endpoints such as mortality,
morbidity (myocardial infarction; stroke)
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Evidence Based Practice
 Looks at the RCT as the standard reference source
 Question is: should this be?
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Uncritical Attitude
 RCT provide the best evidence
 RCT is intrinsically superior
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Historical
 RCT emerged in the mid 1960’s
 Intent: to follow the process of drug development
and evaluation
 Therefore a drug was determined to be safe and
effective, prior to planning and implementing a
clinical trial
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However
 Much must be known about a drug before a clinical
trial can be designed and implemented
 In particular, selecting the right subjects, choosing
an optimal dose, and developing a protocol
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Issues
 Over-valuing the statistical aspects of research
 Under-valuing clinical knowledge
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Random Assignment
 RCT control confounding by randomly assigning large
numbers of subjects to groups;
 Note: never before have RCT involved so many
subjects
 Thus, even the most modest differences between
groups are significant
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To Attract Large Samples
 Protocols are simplified: meaning,
inclusion/exclusion criteria are relaxed
 Reason: need mega samples to detect even the
smallest differences
 Large sample clinical trials, gained by relaxing
criteria, sacrifice experimental control
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Underlying Assumptions of the
RCT of Today
 Primary imperative is recruitment of large numbers
of subjects
 Extrapolation beyond the trial to clinical practice
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Difference Statistics
 Large samples increase statistical power
 Even small differences are significant
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