2. Learning Objectives
• Classify study designs
• Define the unique features of the study
designs
• Discuss weaknesses and strengths
associated with each study design
• Discuss the most appropriate study design
to answer certain research questions
3. Determining a study design
• Identify topic of
interest
• State question of
interest
• State objectives of
the study
• Choose the best
design to answer
question
Topic
Research
question
Objectives
(Hypothesis)
4. Types of Study Designs
Observational
• -- Case report
• -- Case series
• -- Ecological Studies
• -- Cross-sectional
• -- Case-control
• -- Cohort
Experimental
• -- Randomized clinical trial
8. Case Report /Case Series
Case
reports
Case
series
Selective by
nature, providing
little information
May help identify
potential health
problems
Uses of case series
and reports
1 patient: Case Report
More patients: Case Series
9. Ecological Studies
Describe disease
occurrence on
population level
Evaluate an association
using the population -not
the individual -as the unit
of analysis.
The rates of disease are
examined in relation to
factors described on the
population level
Example: Association between
cancer and fat intake?
National Cancer Rate
High Low
High Low
National Diet Fat-Intake
10. Ecological Studies Key issues
Ecological fallacy: We do not know if the individuals who
have cancer were also the individuals with the high fat intake
• Explores correlations between group level exposure
and outcomes
• Unit of analysis: usually not individual, but clusters
(e.g. countries, counties, schools)
• Useful for generating hypothesis
• Cannot adjust well for confounding due to lack of
comparability (due to lack of data on all potential
covariates)
• Missing data is another concern
12. Types of ecological studies
• Multiple group study
Compares disease rates among many regions during the
same period
• Time-trend studies
Comparison of disease rates over time in one population
• Mixed designs
Multiple groups + multiple time periods
15. Uses of ecological studies
• Are appropriate designs when generating
• May be used for testing a new hypothesis
BUT have limited value due to in-built
design errors
• Only design possible when adequate
measurement of individual-level variables
is not possible/not ethical Example:
Holding off immunization
• When funds or time is limited to do
individual level studies
16. Advantages of ecological studies
• Are low cost and convenience
• Simple to analyze and present
• Often helpful for generating new hypotheses for
further research
• Aggregated data on exposure and health outcomes
often publicly available in state and national
databases
17. Disadvantages of ecological studies
• Cannot adjust well for confounding due to lack of
data on all potential covariates
• Measures of exposure are only a proxy based on the
average in the population
• Lack of available data on confounding factors.
• Missing data is another concern
• Prone to Ecological fallacy: We do not know if
grouped results apply on the individual level
18. Ecological fallacy
• Also called ecological inference fallacy or population
fallacy
• is an error where conclusions are inappropriately
inferred about individuals from the results of aggregate
data
• Example: If countries with more Protestants tend to
have higher suicide rates, then Protestants must be
more likely to commit suicide
• How can it be avoided: If individual data is not
available difficult to control for except through
modelling
19. Why ecological studies
• Low cost and convenience
• Some measurements cannot be made on individuals
• Ecologic effects are the main interest (at the
population level)
• Simplicity of analyses and presentation
• Often helpful for generating new hypotheses for
further research
20. Cross-sectional studies
• Exposure and disease are determined
simultaneously for each person a snapshot of
the population at one point in time
• No follow up in this design
• This can only indicate association, but cannot give
a time-sequence.
• Good for prevalence studies and testing
association
21.
22.
23. Strengths
• Fast
• Inexpensive
• May answer question of interest
• Used to determine both prevalence of outcomes and
exposures
• May be used to design future studies
• Start of cohort study
• May even be used for repeat cross-sectional analyses
24. Weaknesses
• Only prevalence cases, can’t measure incidence
• Cannot determine whether exposure preceded
outcome (Outcome may precede exposure)
• Unable to establish causal relations – need for
longitudinal study designs
25. Case-Control study
Start: Cases and Control
Population
Cases
(with
disease)
Controls
(Without
disease)
Exposed
Non-
Exposed
Non-
Exposed
Exposed
Direction of inquiry
Present
Past
26. Case-Control study
• Compares cases to
controls in order find
out what factors are
associated and could
possibly have
contributed to the
problem
• Cases: Diseased
• Controls: Not diseased
• Association measure =
OR
27. Features of case control studies
• Less expensive than cohort studies and
experiments
• Small number of participants needed
• Bes t design for diseases with long latent period
• Very efficient for rare diseases
• Multiple etiologic factors can be studied at one time
• Cannot yield estimates of incidence or prevalence
• Riskier due to biases (especially recall bias)
28. Cohort studies
• A cohort is a group of subjects that are followed
over time starting at a specified point in time and
usually have something in common at the start
• Cohort study is where participants are selected
with respect to exposure
• Individuals exposed to a risk factor (study group)
are compared those not exposed (the control
group).
• Starts with measuring exposure, looks forward to
the outcome
29. Cohort cont….
Purpose
• To study incidence of
disease or other
conditions
• To study associations
between exposures
and outcomes (risk
factors,
determinants)
Measure association
= OR /RR
30. Nested Case-Control Study
Special case-control study and is within an ongoing
cohort study
advantage:
no recall bias, temporal relation between exposure and disease
possible, on selected group of persons more expensive test can be
performed
31. WHY OBSERVATIONAL STUDIES
• Usually the only option if the predictor is a
potentially harmful exposure or risk factor
• Even if the predictor is an intervention, an RCT may
not be feasible due to duration between exposure
and outcome
• Financial reasons: intervention studies can be
significantly more expensive than observational studie
• More intellectually interesting than RCTs?
35. Clinical Trial: Definition
A clinical trial is a prospective study comparing the
effect of intervention(s) against a control
A research activity that involves the administration of
a test regimen
Note: A proper clinical trial
Always prospective
Must have 1 or more interventions
Must have a control group
36.
37. Clinical Trial Objectives
• To asses the efficacy of a new intervention or drug
• To asses the effectiveness of a new intervention or
drug
• To asses the safety of a new intervention or drug
38. History of Clinical Trials
• Daniel 1:12-16. A diet experiment (Royal food and wine versus
vegetables and water) for 10 days
• 17th century: Lancaster (captain of a ship)
– experiment to examine the effect of lemon juice on scurvy for sailors.
– Ships with lemons were free of scurvy compared to ships without
lemons having scurvy.
• Lind (1753) – Study of 5 tx for scurvy in 10 pts (2/tx) plus 2 pts
without tx (control).
– First two pts given orange and lemons recovered quickly and was fit for
duty after 6 days, compared favorably with all other patients
• Smallpox experiment (1721) at the Newgate prison in Great
Britain. Voluntary inmates were inoculated and were free from
smallpox.
39. Key Elements of a Clinical Trial
• Selection of subjects
• Allocation of exposure
• Blinding
• Data collection
• Statistical issues
• Ethical considerations
40. Selection of Subjects
Population at risk/Target population
ENTIRE group of individuals to generalize results
The intervention is intended to benefit this population
Accessible population
Population to which the researcher has reasonable access
May be a subset of the target
Study population
Group of participants actually studied
Subset of population meeting eligibility criteria
Inclusion criteria – identifies the target population
Exclusion criteria – excludes people from the study, mainly for
safety reasons
41. Allocation of exposure
• Studies without controls –
not a clinical trial although still an experiment
• Studies with controls: Types of controls/Comparison groups
Historical controls (compare with the past)
Simultaneous non-randomized controls (concurrent
group/quasi experiment)
Randomization - true controls
• Importance of controls
For comparisons
Allow to determine if outcome is caused by intervention vs
other factors
42. Randomized controlled Trials (RCT)
• Exposure assigned in a random way, participant have
equal chance of being in either control or intervention
group
• Balances the known and unknown risk factors for the
outcome under study
– eliminates confounding due to measured and unmeasured
factors
• Methods for randomization
Simple randomization (fish bowel method, tossing a coin)
Random number table
Computer-generated list of assignments
43. Blinding/ Masking
• The team assessing the outcome are not aware of
treatment assignment
• To prevent the biased assessment of the outcome
Single-blinded study
• Either pts or physicians are blinded to the tx
allocation
Double-blinded study
• Both pts and physicians are blinded to the tx
allocation
44. Analysis of trials
• Should always start with a baseline comparison of
groups
Note: Investigator cannot dictate what a participant does
in a clinical trial, may or may not comply with Rx
Intent-to-treat (ITT)
– Participants are analyzed according to the groups they were
randomized
– If 100 randomized to a treatment, all analysed whether took
it or not
Per-protocol analysis
• Analysis is only for participants who completed the treatment
Both analyses are recommended and compare
conclusions
45. Phases of Clinical Trials
• Phase I: clinical pharmacology and toxicity
– 1st experiment in human for new drug
– Primary concern: Safety
– Typically required 15-30 patients
• Phase II: Initial Assessment of Efficacy
– examine the efficacy and refine the safety
– Goal is to screen out ineffective drugs
– Has 30-100 participants
• Phase III: Full-scale Evaluation of Treatment Efficacy
– Compare new treatment with standard treatment
– Aim is to define the ‘best’ treatment
– Hundreds to thousands of participants
• Phase IV: Postmarking Surveillance
– monitoring the adverse effects
46. Ethical Principles in Trials
• Respect for Persons
– Voluntary, informed consent
– Protection of vulnerable populations
– Right to end participation in research at any time
– Right to safeguard integrity
– Protection of privacy and well-being
• Beneficence
– Non-malfeasance
– Benefits should outweigh cost/risks
• Justice
– Protection from physical, mental and emotional harm
– Fairness
ALL TRIALS MUST BE REGISTERED IN A CLINICAL TRIAL REGISTRY
